invasion

Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein is an E3 ubiquitin ligase that interferes with host's ubiquitination pathway and modulates the acute inflammatory responses, thus facilitating bacterial colonization within the host cell. IpaH9.8 Protein, Shigella flexneri, Recombinant (His) is expressed in yeast with N-6xHis tag. The predicted molecular weight is 64.0 kDa and the accession number is D2AJU0.

FGF6, also known as FGF-6, belongs to the fibroblast growth factor (FGF) family. Members of this family possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF6 plays an important role in the regulation of cell proliferation, cell differentiation, angiogenesis and myogenesis. It is also required for normal muscle regeneration. FGF6 gene displayed oncogenic transforming activity when transfected into mammalian cells.

TPPP3, a member of the Tubulin polymerization-promoting protein family, is an intrinsically unstructured protein that induces tubulin polymerization. TPPP3 is a marker in the developing musculoskeletal system. In tendons, Tppp3 is expressed in cells at the circumference of the developing tendons, likely the progenitors of connective tissues that surround tendons: the tendon sheath, epitenon, and paratenon. Tppp3 is also expressed in forming synovial joints. The onset of Tppp3 expression in joints coincides with cavitation, representing a molecular marker that can be used to indicate this stage in joint transition in joint differentiation. In late embryonic stages, Tppp3 expression highlights other demarcation lines that surround differentiating tissues in the forelimb. Depletion of TPPP3 by microRNA-based RNA interference (RNAi) inhibits cell growth, arrests cell cycles, and causes mitotic abnormalities in HeLa cells. C57BL/6 mice that received subcutaneously injected LLC (Lewis lung carcinoma) cells in which TPPP3 was knocked down showed a pronounced reduction in tumor progression. The migration/invasion activity of TPPP3-knockdown LLC cells was significantly suppressed in a transwell chamber migration assay. When these cells were injected into the tail veins of C57BL/6 mice, they exhibited milder lung metastasis compared with control tumor cells. Taken together, these findings suggested that the TPPP3 gene played an important role in tumorigenesis and metastasis, and it could potentially become a novel target for cancer therapy.

Angiopoietin-like protein 1 (ANGPTL1) has been reported to suppress migration and invasion in lung and breast cancer, acting as a novel tumor suppressor candidate. Downregulation of tumor suppressor signaling plays an important role in the pathogenesis of hepatocellular carcinoma (HCC).The downregulation of the angiopoietin-like protein ANGPTL1 is associated with vascular invasion, tumor thrombus, metastasis, and poor prognosis in HCC. Ectopic expression of ANGPTL1 in HCC cells effectively decreased their in vitro and in vivotumorigenicity, cell motility, and angiogenesis. shRNA-mediated depletion of ANGPTL1 exerted opposing effects. ANGPTL1 promoted apoptosis via inhibition of the STAT3/Bcl-2-mediated antiapoptotic pathway and decreased cell migration and invasion via downregulation of transcription factors SNAIL and SLUG. Furthermore, ANGPTL1 inhibited angiogenesis by attenuating ERK and AKT signaling and interacted with integrin α1β1 receptor to suppress the downstream FAK/Src-JAK-STAT3 signaling pathway. Taken together, these results suggest ANGPTL1 as a prognostic biomarker and novel therapeutic agent in HCC. ANGPTL1 expression was down-regulated in CRC tissues and inversely correlated with poor survival. ANGPTL1 repressed migration and invasion of CRC cells, and microRNA-138 was involved in this process. Angiopoietin-like protein 1 (ANGPTL1) has been shown to act as a tumor suppressor by inhibiting angiogenesis, cancer invasion, and metastasis.

72 kDa type IV collagenase also known as matrix metalloproteinase-2 (MMP-2) and gelatinase A is an enzyme that in humans is encoded by the MMP2 gene.It belongs to the matrix metalloproteinase (MMP) family. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that degrade components of the extracellular matrix (ECM) and play essential roles in various physiological processes such as morphogenesis, differentiation, angiogenesis and tissue remodeling, as well as pathological processes including inflammation, arthritis, cardiovascular diseases, pulmonary diseases and tumor invasion. MMP-2 is ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, atherosclerotic plaque rupture, as well as degrading extracellular matrix proteins. MMP-2 can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. MMP-2 cleaves KISS at a Gly-|-Leu bond and appears to have a role in myocardial cell death pathways.

Serpin A5 is a member of the human Serpin superfamily consists of at least 35 members. It is synthesized in the liver and has been detected in saliva, cerebral spinal fluid, amniotic fluid, tears and semen. As a potent inhibitor of the protein C anticoagulant pathway at the levels of both zymogen activation and enzyme inhibition, Serpin A5 additionally inhibits a variety of serine protease including thrombin, factor Xa, several kallekreins and acrosin. It plays a critical role in the processes of blood of blood coagulation and fertilization. Serpin A5 also inhibits urinary plasminogen activator (uPA), a mediator of tumor cell invasion, and regulates tumor growth and metastasis by inhibiting angiogenesis. Furthermore, recent studies have identified PCI as a potent and direct inhibitor of activated HGFA (hepatocyte growth factor activator), suggesting a novel function in the regulation of tissue repair and regeneration. Similar to Serpins C1 and D1, the thrombin inhibitory activity of serpinA5 is enhanced by heparin.

Axl, a member of the TAM (Tyro3, Axl, Mer) family, and its inhibitors can specifically break the kinase signaling nodes, allowing advanced patients to regain drug sensitivity with improved therapeutic efficacy. Overexpression and activation of Axl receptor tyrosine kinase have been widely accepted to promote cell proliferation, chemotherapy resistance, invasion, and metastasis in several human cancers, such as lung, breast, and pancreatic cancers. AXL Protein, Human, Recombinant (His & Avi), Biotinylated is expressed in HEK293 mammalian cells with C-His-Avi tag. The predicted molecular weight is 48.7 kDa and the accession number is P30530-1.

Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. The tyrosine kinase receptor vascular endothelial growth factor receptor 2 (VEGFR2) is a key regulator of angiogenesis. VEGFR2/KDR Protein, Human, Recombinant (His & Avi) is expressed in HEK293 mammalian cells with C-His-Avi tag. The predicted molecular weight is 86.2 kDa and the accession number is P35968-1.

EphB2, a receptor tyrosine kinase for ephrin ligands, is overexpressed in various cancers and plays an important role in tumor progression. EPHB2 promotes endothelial-mesenchymal transition (EMT) and elicits associated pathologic characteristics of glioblastoma multiforme (GBM) such as invasion and migration. EPHB2 is epigenetically overexpressed in hypoxia, a condition highly prevalent in malignancy. Furthermore, HIF-2α is required for EPHB2 stabilization by hypoxia.

Ectonucleotide pyrophosphatase-phosphodiesterase 3 (ENPP3), a protein detected in the human uterus, has been found to play an important role in the development and invasion of tumours. It was recently discovered that ENPP3 was upregulated during the window of implantation in the human endometrium but its functional relevance remains elusive. ENPP3 Protein, Human, Recombinant (aa 48-157, His & Avi) is expressed in HEK293 mammalian cells with N-His-Avi tag. The predicted molecular weight is 17.21 kDa and the accession number is O14638.

E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins, such as CD3D, CYP3A4, CFTR, INSIG1, SOAT2/ACAT2 and APOB for proteasomal degradation. Component of a VCP/p97-AMFR/gp78 complex that participates in the final step of endoplasmic reticulum-associated degradation (ERAD). The VCP/p97-AMFR/gp78 complex is involved in the sterol-accelerated ERAD degradation of HMGCR through binding to the HMGCR-INSIG1 complex at the ER membrane. In addition, interaction of AMFR with AUP1 facilitates interaction of AMFR with ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase RNF139, leading to sterol-induced HMGCR ubiquitination. The ubiquitinated HMGCR is then released from the ER into the cytosol for subsequent destruction. In addition to ubiquitination on lysine residues, catalyzes ubiquitination on cysteine residues: together with INSIG1, mediates polyubiquitination of SOAT2/ACAT2 at 'Cys-277', leading to its degradation when the lipid levels are low. Catalyzes ubiquitination and subsequent degradation of INSIG1 when cells are depleted of sterols. Mediates polyubiquitination of INSIG2 at 'Cys-215' in some tissues, leading to its degradation. Also regulates ERAD through the ubiquitination of UBL4A a component of the BAG6/BAT3 complex. Also acts as a scaffold protein to assemble a complex that couples ubiquitination, retranslocation and deglycosylation. Mediates tumor invasion and metastasis as a receptor for the GPI/autocrine motility factor. In association with LMBR1L and UBAC2, negatively regulates the canonical Wnt signaling pathway in the lymphocytes by promoting the ubiquitin-mediated degradation of CTNNB1 and Wnt receptors FZD6 and LRP6.

Required for invasion of epithelial cells.

Required for invasion of epithelial cells. PrgJ Protein, Salmonella typhimurium, Recombinant (Yeast, His & Myc) is expressed in yeast with N-6xHis and C-Myc tag. The predicted molecular weight is 14.4 kDa and the accession number is P41785.

Important streptococcal virulence factor which cleaves human fibronectin and degrades vitronectin. Also cleaves human IL1B precursor to form biologically active IL1B. Can induce apoptosis in human monocytes and epithelial cells in vitro, and reduces phagocytic activity in monocytic cells. Thus, may play a role in bacterial colonization, invasion, and inhibition of wound healing. Streptopain Protein, S. pyogenes serotype M28, Recombinant (His & SUMO) is expressed in E. coli expression system with N-6xHis-SUMO tag. The predicted molecular weight is 43.6 kDa and the accession number is Q48R29.

Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell proliferation. Collagen binding triggers a signaling pathway that involves SRC and leads to the activation of MAP kinases. Regulates remodeling of the extracellular matrix by up-regulation of the matrix metalloproteinases MMP2, MMP7 and MMP9, and thereby facilitates cell migration and wound healing. Required for normal blastocyst implantation during pregnancy, for normal mammary gland differentiation and normal lactation. Required for normal ear morphology and normal hearing. Promotes smooth muscle cell migration, and thereby contributes to arterial wound healing. Also plays a role in tumor cell invasion. Phosphorylates PTPN11.

PFDN1 expression positively correlated with tumor size and tumor invasion. The inhibitory effect of PFDN1 on tumor cell growth and motility was partially due to G2/M cell cycle blockage and cytoskeletal deficiency. PFDN1 was involved in the progression of CRC, and provide new insights into PFDN1 as a potential therapeutic target for colorectal cancer (CRC) treatment. PFDN1 Protein, Human, Recombinant (His) is expressed in E. coli expression system with His tag. The predicted molecular weight is 16 kDa and the accession number is O60925.

LAP3 (Leucine Aminopeptidase 3) is a Protein Coding gene. 2 alternative initiation human isoforms have been reported. LAP3, belonging to the peptidase M17 family, has been proved to catalyze the hydrolysis of leucine residues. It catalyzes the removal of unsubstituted N-terminal amino acids from various peptides and is presumably involved in the processing and regular turnover of intracellular proteins. Leucine aminopeptidases are involved in many pathological disorders and regulate cell proliferation, invasion, and/or angiogenesis of tumors. A recent study showed that LAP3 is highly expressed in several malignant and affects tumor angiogenesis. LAP3 is widely expressed in the appendix, lymph node, and other tissues. Diseases associated with LAP3 include Bacterial Vaginosis and Trichomoniasis.

v-akt murine thymoma viral oncogene homolog 1 (AKT1), or protein kinase B-alpha (PKB-ALPHA) is a serine-threonine protein kinase, belonging to the Protein Kinase Superfamily. AKT1 is a major mediator of the responses to insulin, insulin-like growth factor 1 (IGF1), and glucose. AKT1 also plays a key role in the regulation of both muscle cell hypertrophy and atrophy. AKT1 activity is required for physiologic cardiac growth in response to IGF1 stimulation or exercise training. In contrast, AKT1 activity was found to antagonize pathologic cardiac growth that occurs in response to endothelin 1 stimulation or pressure overload. AKT1 selectively promotes physiological cardiac growth while AKT2 selectively promotes insulin-stimulated cardiac glucose metabolism. AKT1 deletion prevented tumor initiation as well as tumor progression, coincident with decreased Akt signaling in tumor tissues. AKT1 is the primary Akt isoform activated by mutant K-ras in lung tumors, and that AKT3 may oppose AKT1 in lung tumorigenesis and lung tumor progression. A number of separate studies have implicated AKT1 as an inhibitor of breast epithelial cell motility and invasion. AKT1 may have a dual role in tumorigenesis, acting not only pro-oncogenically by suppressing apoptosis but also anti-oncogenically by suppressing invasion and metastasis.Cancer ImmunotherapyImmune CheckpointImmunotherapyTargeted Therapy

The three butyrophilin BTN3A molecules, BTN3A1, BTN3A2, and BTN3A3, are members of the B7/butyrophilin-like group of Ig superfamily receptors, which modulate the function of T cells. BTN3A2 is overexpressed in gastric tumors, and deletion of BTN3A2 inhibited proliferation, migration, and invasion of gastric cancer cells. The butyrophilin 3 (BTN3) receptors are implicated in the T lymphocytes regulation and present a wide plasticity in mammals. A thorough phylogenetic analysis reveals a concerted evolution of BTN3 characterized by a strong and recurrent homogenization of the region encoding the signal peptide and the immunoglobulin variable (IgV) domain in Hominoids, where the sequences of BTN3A1 or BTN3A3 are replaced by BTN3A2 sequence.

Fibroblast Growth Factor 9 (FGF-9) belongs to the Fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF-9 plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. In addition, FGF-9 may have a role in glial cell growth and differentiation during development, gliosis during repair and regeneration of brain tissue after damage, differentiation and survival of neuronal cells, and growth stimulation of glial tumors.

Fibroblast Growth Factor 17 (FGF17) is a member of the heparin-binding growth factors family that is prominently expressed in the cerebellum and cortex. Proteins of this family possess broad mitogenic and cell survival activities and they are involved in a variety of biological processes including embryonic development cell growth, morphogenesis, tissue repair, tumor growth, and invasion. FGF17 plays an important role in the regulation of embryonic development and it acts as signaling molecule in the induction and patterning of the embryonic brain. In addition, FGF17 stimulates the proliferation and activation of cells that express FGF receptors.

CD82 antigen, also known as Kai-1, is a widely expressed palmitoylated molecule of the tetraspanin superfamily. KAI1/CD82 is localized on cell membrane and form interactions with other tetraspanins, integrins and chemokines which are respectively responsible for cell migration, adhesion and signaling. CD82/Kai-1 is a component of the promiscuous TIMP-1 interacting protein complex on the cell surface of human adenocarcinoma cells and gives insight into tumorigenic metastatic potential. CD82/Kai-1 suppresses EMT in prostate cancer cells adhered to fibronectin leading to reduced cell migration and invasiveness. CD82/Kai-1 function is important for muscle stem cell function in muscular disorders. Overexpression of CD82/Kai-1 suppresses growth, migration and invasion of oral cancer cells and may be considered as a potential therapeutic target in oral cancer.

Acidic Fibroblast Growth Factor Intracellular-Binding Protein (FIBP) is highly expressed in the heart, skeletal muscle, and pancreas. Acidic Fibroblast Growth Factor is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FIBP is an intracellular protein that binds selectively to acidic fibroblast growth factor (aFGF). It is postulated that FIBP may be involved in the mitogenic action of aFGF.

Programmed Cell Death Protein 4 (PDCD4) is a member of the PDCD4 family. PDCD4 and EIF4A1 form a heterotrimer. One molecule of PDCD4 binds two molecules of EIF4A1. PDCD4 takes part in apoptosis via inhibiting translation initiation and cap-dependent translation.PDCD4 promotes colonic neoplastic transformation and tumor invasion. PDCD4 is an important target for microrna R-21 in breast cancer cells. Shortage of PDCD4 expression is associated with colorectal cancer. Overexpression of PDCD4 in carcinoid cells results in inhibition of cell proliferation.

CD155 is a cell surface adhesion molecule functioning in tumor cell migration, invasion, and metastasis, and not surprisingly, is also designated as a common tumor-associated antigen. CD155 is also recognized by NK cells to induce their cytotoxicity. CD155 is also commonly referred to as the poliovirus receptor, or PVR.

Ectonucleotide pyrophosphatase-phosphodiesterase 3 (ENPP3), a protein detected in the human uterus, has been found to play an important role in the development and invasion of tumours. It was recently discovered that ENPP3 was upregulated during the window of implantation in the human endometrium but its functional relevance remains elusive. ENPP3 Protein, Human, Recombinant (His & Avi) is expressed in HEK293 mammalian cells with N-His-Avi tag. The predicted molecular weight is 99.97 kDa and the accession number is O14638.

CD164 was found to play a role in many malignant diseases. CD164 was associated with clinical and pathological features of patients. High level of CD164 was related to the distant metastasis and vascular invasion of bladder cancer patients.CD164 was associated with the poor clinical outcomes of BC patients. Silencing of CD164 could inhibit the progression of tumors in vivo and in vitro, which may become an effective target in the treatment of bladder cancer. CD164 Protein, Human, Recombinant (hFc) is expressed in HEK293 mammalian cells with C-hFc tag. The predicted molecular weight is 41.2 kDa and the accession number is Q04900-1.

Transversalis fascia EFEMP1, TIMP3 and ELN expressions were decreased, but MMP9 expression was increased in IH patients compared with controls. In IH patients, EFEMP1 was not correlated with TIMP3, but positively correlated with ELN and negatively correlated with MMP9; TIMP3 negatively correlated with MMP9, but positively correlated with ELN.In addition, EFEMP1 suppressed L929 cell migration and invasion. EFEMP1 Protein, Mouse, Recombinant (His) is expressed in HEK293 mammalian cells with N-His tag. The predicted molecular weight is 54.1 kDa and the accession number is Q8BPB5.

Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis. Cathepsin F Protein, Human, Recombinant (His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 27.4 kDa and the accession number is Q9UBX1.

Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.

Fibroblast growth factor 10 (FGF10) is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF10 exhibits mitogenic activity for keratinizing epidermal cells, but essentially no activity for fibroblasts, which is similar to the biological activity of FGF7. FGF10 plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation. FGF10 is required for normal branching morphogenesis. It may play a role in wound healing. Defects in FGF10 are the cause of autosomal dominant aplasia of lacrimal and salivary glands (ALSG). ALSG has variable expressivity, and affected individuals may have aplasia or hypoplasia of the lacrimal, parotid, submandibular and sublingual glands and absence of the lacrimal puncta. The disorder is characterized by irritable eyes, recurrent eye infections, epiphora (constant tearing) and xerostomia (dryness of the mouth), which increases the risk of dental erosion, dental caries, periodontal disease and oral infections.

S100 protein is a family of low molecular weight protein found in vertebrates characterized by two EF-hand calcium-binding motifs. There are at least 21 different S100 proteins, and the name is derived from the fact that the protein is 100% soluble in ammonium sulfate at neutral pH. Most S100 proteins are disulfide-linked homodimer, and is normally present in cells derived from the neural crest, chondrocytes, macrophages, dendritic cells, etc. S1 proteins have been implicated in a variety of intracellular and extracellular functions. They are involved in regulation of protein phosphorylation, transcription factors, the dynamics of cytoskeleton constituents, enzyme activities, cell growth and differentiation, and the inflammatory response. Protein S100-A10, also known as Calpactin I light chain, Cellular ligand of annexin II, S100 calcium-binding protein A10, p10 protein, p11, ANX2LG and S100A10, is a member of the S100 family of small, dimeric EF hand-type Ca(2+)-binding proteins that generally modulate cellular target proteins in response to intracellular Ca(2+) signals. In contrast to all other S100 proteins, S100A10 is Ca(2+) insensitive because of amino acid replacements in its Ca(2+)-binding loops that lock the protein in a permanently active state. S100A10 forms a heterotetramer with annexin IIH and promotes carcinoma invasion and metastasis by plasminogen activation. S100A10 and annexin II contribute to the aggressive characteristics of anaplastic carcinoma, while playing a constitutive role in papillary carcinoma. S100A10 induces the dimerization of ANXA2 / p36, it may function as a regulator of protein phosphorylation in that the ANXA2 monomer is the preferred target of tyrosine-specific kinase. S100A10 functions as a linker tethering certain transmembrane proteins to annexin A2 thereby assisting their traffic to the plasma membrane and/or their firm anchorage at certain membrane sites.

SEMA6A, the first identified class 6 semaphorin, is contributed to regulate vascular development and adult angiogenesis. SEMA6A could inhibit proliferation, migration, and invasion in different glioma cell lines. That SEMA6A may be a potential prognostic biomarker in the treatment of GBM. Among different semaphorins tested by reverse transcriptase-polymerase chain reaction in human immune cells, the expression of class 6 transmembrane semaphorin SEMA6A was restricted to dendritic cells (DCs).

p53, also known as Tp53, is a DNA-binding protein which belongs to the p53 family. It contains transcription activation, DNA-binding, and oligomerization domains. p53 protein is expressed at low level in normal cells and at a high level in a variety of transformed cell lines, where it's believed to contribute to transformation and malignancy. p53 (TP53) is a transcription factor whose protein levels and post-translational modification state alter in response to cellular stress (such as DNA damage, hypoxia, spindle damage). Activation of p53 begins through a number of mechanisms including phosphorylation by ATM, ATR, Chk1 and MAPKs. MDM2 is a ubiquitin ligase that binds p53 and targets p53 for proteasomal degradation. Phosphorylation, p14ARF and USP7 prevent MDM2-p53 interactions, leading to an increase in stable p53 tetramers in the cytoplasm. Further modifications such as methylation and acetylation lead to an increase in Tp53 binding to gene specific response elements. Tp53 regulates a large number of genes (>100 genes) that control a number of key tumor suppressing functions such as cell cycle arrest, DNA repair, senescence and apoptosis. Whilst the activation of p53 often leads to apoptosis, p53 inactivation facilitates tumor progression. It is postulated to bind to a p53-binding site and activate expression of downstream genes that inhibit growth and/or invasion, and thus function as a tumor suppressor. Mutants of p53 that frequently occur in a number of different human cancers fail to bind the consensus DNA binding site, and hence cause the loss of tumor suppressor activity. Defects in TP53 are a cause of esophageal cancer, Li-Fraumeni syndrome, lung cancer and adrenocortical carcinoma.Cancer ImmunotherapyImmune CheckpointImmunotherapyTargeted Therapy

Osteosarcoma (OS) is the most common type of bone tumor in children and adults. The expression of APCDD1, a Wnt antagonist, was reduced in OS tissues and cells compared to adjacent normal tissue and osteoblast cells, respectively. Mechanistically, this was due to increased levels of methylation in the promoter region of the APCDD1 gene. Consistently, the DNA methyltransferase inhibitor 5-AZA-dC, reduced DNA methylation in the APCDD1 promoter, and restored APCDD1 expression in OS tissue and cells. Moreover, DNMT3a, but not DNMT1 or DNMT3b, was the major DNA methyltransferase that facilitated hyper-methylation of DNA in the APCDD1 promoter, thus reducing APCDD1 mRNA levels in OS tissues. Importantly, ectopic expression of APCDD1 suppressed activity of the Wnt/beta-Catenin signaling pathway in OS cells and inhibited their invasion and reversed their EMT-like properties, while depletion of APCDD1 promoted invasion and metastasis of osteosarcoma cells in vitro and in vivo. That APCDD1 modulates the gene expression of Wnt- and EK-related signaling molecules at the cap stage of tooth development, and is involved in tooth cusp patterning by modulating the epithelial rearrangement in the IEE. In hair follicle cells APCDD1 inhibits the canonical WNT/beta-Catenin pathway and its inactivation is associated with an autosomal dominant form of hair loss. APCDD1 sustains the expression and activation of beta-Catenin.

The growth arrest-specific 6 gene (GAS6) is a member of the family of plasma vitamin K-dependent proteins, which are able to bind to phospholipids using an N-terminal gamma-carboxyglutamic acid domain. GAS6 is a vitamin K-dependent protein, plays a role in the survival, proliferation, migration, differentiation, adhesion, and apoptosis of cells. The growth arrest-specific 6 (GAS6) has been implicated in systemic inflammation and coagulation. Growth arrest-specific 6 (GAS6), plays a role in tumor progression by regulating growth in many cancers. GAS6, expressed by osteoblasts in the bone marrow, plays a significant role in the regulation of PCa cell survival during chemotherapy, which will have important implications for targeting metastatic disease. The GAS6/TYRO3-AXL-MERTK (TAM) signaling pathway is essential for full and sustained platelet activation, as well as thrombus stabilization. Inhibition of this pathway decreases platelet aggregation, shape change, clot retraction, aggregate formation under flow conditions, and surface expression of activation markers. It had been show that GAS6 signaling regulates invasion, proliferation, chemotherapy-induced apoptosis of prostate cancer (PCa) cells, and GAS6 secreted from osteoblasts in the bone marrow environment plays a critical role in establishing prostate tumor cell dormancy.

FGF12 is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. FGF12 lacks the N-terminal signal sequence present in most of the FGF family members, but it contains clusters of basic residues that have been demonstrated to act as a nuclear localization signal. When transfected into mammalian cells, FGF12 accumulated in the nucleus, but was not secreted. The specific function of FGF12 gene has not yet been determined. Two alternatively spliced transcript variants encoding distinct isoforms have been reported.

Eukaryotic translation initiation factor 5A2 (EIF5A2) has been demonstrated to be upregulated in numerous types of human cancer and is associated with cancer progression. Silencing of EIF5A2 in the NSCLC cells resulted in the downregulation of the tumorigenic proteins, apoptosis regulator Bcl-2 and myc proto-oncogene protein, and upregulation of E-cadherin, suggesting that EIF5A2 promotes proliferation and metastasis through these proteins. EIF5A2 may therefore serve as a novel therapeutic target for the treatment of NSCLC. EIF5A2 might be a novel therapeutic target for the inhibition of NPC progress. EIF5A2 overexpression may contribute to cancer progression and poor prognosis, it could be a novel potential prognostic marker for FIGO stage I-II cervical cancer. EIF5A2 upregulation plays an important oncogenic role in gastric cancer. EIF5A2 may represent a new predictor for poor survival and is a potential therapeutic target for gastric cancer. The eukaryotic initiation factor 5A2 (EIF5A2) over-expression enhances HCC cell metastasis. EIF5A2, as a target of PI3K/Akt, promotes melanoma cell invasion and may serve as a promising prognostic marker and a potential therapeutic target for melanoma.

AKT (AK mouse plus Transforming or Thymoma) is a frequent oncogene expressed in most tissues which includes three isoforms AKT1, AKT2, and AKT3. Hyperactivation of AKT signaling is a central key in many human cancer progressions, through modulating angiogenesis, tumor growth, and cell migration, invasion, metastasis, and chemoresistance. Among all three isoforms, AKT2 is most related to cancer cell invasion, metastasis, and survival. Amplification and overexpression of AKT2 have been shown in many cancers. Accumulating evidence shows the potential role of different miRNA involvements in cancer progression by activating or suppressing AKT2 expression. The AKT2/NAB1/SPK1 pathway is a novel regulating factor of macrophage migration and cardiac remodeling after myocardial infarction. The novel mechanism of the AKT2-PKM2-STAT3/NF-kappaB axis in the regulation of ovarian cancer progression, that both AKT2 and PKM2 may be potential targets for the treatment of ovarian cancer. AKT1 and AKT2, the AKT isoforms that are highly expressed in skeletal muscle, have distinct and overlapping functions, with AKT2 more important for insulin-stimulated glucose metabolism. In adipocytes, AKT2 versus AKT1 has greater susceptibility for insulin-mediated redistribution from cytosolic to membrane localization, and insulin also causes subcellular redistribution of AKT Substrate of 160 kDa (AS160), an AKT2 substrate and crucial mediator of insulin-stimulated glucose transport.

Cathepsin L is an enzyme. Cathepsin L, a lysosomal endopeptidase expressed in most eukaryotic cells, is a member of the papain-like family of cysteine proteinases. Cathepsin L plays a major role in antigen processing, tumor invasion and metastasis, bone resorption, and turnover of intracellular and secreted proteins involved in growth regulation. Unlike the precursor forms of other papain family members, the 43 kDa pro-cathepsin L itself is secreted from various cells. Pro-cathepsin L is the major excreted protein of malignantly transformed mouse fibroblasts and is also one of the major acidic cysteine proteases in mammalian cells.

Serine Protease Inhibitor Kazal-Type 1 (SPINK1) is a trypsin inhibitor that prevent the trypsin-catalyzed premature activation of zymogens within the pancreas. Defects in SPINK1 are a cause of pancreatitis (PCTT). A disease characterized by the presence of calculi in pancreatic ducts. It causes severe abdominal pain attacks. Defects in SPINK1 are the cause of susceptibility to tropical calcific pancreatitis (TCP). Recombinant SPINK1 protein (rSPINK1) stimulated cell proliferation in benign RWPE as well as cancerous prostate cells. The research result indicated that the potential of SPINK1 as an extracellular therapeutic target in prostate cancer. In contrast, knockdown of SPINK1 in 22RV1 cells inhibited cell proliferation, cell invasion, and tumor growth in xenograft assays.

Axl, a member of the TAM (Tyro3, Axl, Mer) family, and its inhibitors can specifically break the kinase signaling nodes, allowing advanced patients to regain drug sensitivity with improved therapeutic efficacy. Overexpression and activation of Axl receptor tyrosine kinase have been widely accepted to promote cell proliferation, chemotherapy resistance, invasion, and metastasis in several human cancers, such as lung, breast, and pancreatic cancers. AXL Protein (Primary Amine Labeling), Human, Recombinant (hFc), Biotinylated is expressed in HEK293 mammalian cells with C-hFc tag. The predicted molecular weight is 72.6 kDa and the accession number is P30530-1.

Placental-Cadherin (CDH3), a cell adhesion molecule, is associated with the function of cells to bind with other cells and the extracellular matrix (ECM). CDH3 is highly expressed in many malignancies, and has been proved it could be a serum marker to monitor colorectal cancer. Inhibited CDH3 expression could upregulate E-cadherin, downregulated N-cadherin, which may control invasion and migration. CDH3 Protein, Mouse, Recombinant (His) is expressed in HEK293 mammalian cells with C-His tag. The predicted molecular weight is 64.68 kDa and the accession number is P10287.

L1 cell adhesion molecule (L1CAM) is one of the first neural adhesion molecules described with important functions in the development of the nervous system. Subsequent work discovered that L1CAM is expressed in many human cancers and is often associated with bad prognosis. This is most likely due to the motility and invasion promoting function of L1CAM. L1CAM is a valuable diagnostic/prognostic marker and an attractive target for the therapy of several human cancers.

Amphiregulin (AREG) is a member of the epidermal growth factor (EGF) family and is expressed in a plethora of cancers. Tumour growth and metastasis were decreased by AREG silencing in an orthotopic model of pancreatic cancer. AREG may play a critical role in cell migration, invasion, and EMT by activating the EGFR/ERK/NF‑κB signalling pathway in pancreatic cancer cells.

Placental-Cadherin (CDH3), a cell adhesion molecule, is associated with the function of cells to bind with other cells and the extracellular matrix (ECM). CDH3 is highly expressed in many malignancies, and has been proved it could be a serum marker to monitor colorectal cancer. Inhibited CDH3 expression could upregulate E-cadherin, downregulated N-cadherin, which may control invasion and migration. CDH3 Protein, Human, Recombinant (aa 108-654, His) is expressed in HEK293 mammalian cells with C-His tag. The predicted molecular weight is 64.32 kDa and the accession number is P22223-1.

Ectonucleotide pyrophosphatase-phosphodiesterase 3 (ENPP3), a protein detected in the human uterus, has been found to play an important role in the development and invasion of tumours. It was recently discovered that ENPP3 was upregulated during the window of implantation in the human endometrium but its functional relevance remains elusive. ENPP3 Protein, Canine, Recombinant (His) is expressed in HEK293 mammalian cells with N-His tag. The predicted molecular weight is 96.19 kDa and the accession number is A0A8I3N0F5.

Placental-Cadherin (CDH3), a cell adhesion molecule, is associated with the function of cells to bind with other cells and the extracellular matrix (ECM). CDH3 is highly expressed in many malignancies, and has been proved it could be a serum marker to monitor colorectal cancer. Inhibited CDH3 expression could upregulate E-cadherin, downregulated N-cadherin, which may control invasion and migration. CDH3 Protein, Cynomolgus, Recombinant (His) is expressed in HEK293 mammalian cells with C-His tag. The predicted molecular weight is 61.11 kDa and the accession number is XP_005592414.1.

Required for bacterial invasion of host cells. Controls IpaB and IpaC secretion, and the efficiency with which they are physically inserted into target cell membranes. These proteins are exported via TTSS to form a pore in the host membrane that allows the translocation of the other effectors into the host cytoplasm. Along with IpaB, is essential for both blocking secretion through the Mxi/Spa translocon in the absence of a secretion-inducing signal, and for controlling the level of secretion in the presence of this signal.

Required for invasion of epithelial cells. PrgJ Protein, Salmonella typhimurium, Recombinant (E. coli, His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 15.9 kDa and the accession number is P41785.