breast tumor

Mucin-1, is a membrane-bound protein that is a member of the mucin family. Mucins are O-glycosylated proteins that play an essential role in forming protective mucous barriers on epithelial surfaces. These proteins also play a role in intracellular signaling. This protein is expressed on the apical surface of epithelial cells that line the mucosal surfaces of many different tissues including lung, breast stomach and pancreas. MUC-1 exclusively located in the apical domain of the plasma membrane of highly polarized epithelial cells. MUC-1 can act both as an adhesion and an anti-adhesion protein. This protein may provide a protective layer on epithelial cells against bacterial and enzyme attack. MUC-1 participated in modulates signaling in ERK, SRC and NF-kappa-B pathways. In activated T-cells, MUC-1 influences directly or indirectly the Ras/MAPK pathway. MUC-1 promotes tumor progression and regulates TP53-mediated transcription and determines cell fate in the genotoxic stress response.

Mucin-1/MUC1 Protein, Human, Recombinant (His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 31.2 kDa and the accession number is P15941-8.

Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A) is also known as TNF-related apoptosis-inducing ligand receptor 1 (TRAIL-R1), Death receptor 4 (DR4), CD261 and APO2, which belongs to TNF superfamily. TNFRSF10A / DR4 is widely expressed and high levels are found in spleen, peripheral blood leukocytes, small intestine and thymus, but also in K-562 erythroleukemia cells, MCF-7 breast carcinoma cells and activated T-cells. APO2 / TNFRSF10A is receptor for the cytotoxic ligand TNFSF10 / TRAIL. This receptor is activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF1/TRAIL), and thus transduces cell death signal and induces cell apoptosis. TRAIL R1 can promote the activation of NF-kappa-B. TRAIL R1/CD261/TNFRSF1A induces apoptosis of many transformed cell lines but not of normal tissues, even though its death domain-containing receptor, DR4, is expressed on both cell types.

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.

C-C motif chemokine 5(CCL5) is a β-chemokine that plays a primary role in the inflammatory immune response by means of its ability to attract and activate leukocytes. CCL5 is secreted by many cell types at inflammatory sites, and it exerts a wide range of activities through the receptors CCR1, CCR3, CCR4, and CCR5. Inflammatory responses can be impaired by the sequestration of CCL5 by the cytomegalovirus protein US28. Oligomerization of CCL5 on glycosaminoglycans is required for CCR1mediated leukocyte adhesion and activation as well as CCL5’s interaction with the chemokine CXCL4/PF4.The deposition of CCL5 on activated vascular endothelial cells is crucial for monocyte adhesion to damaged vasculature, but CCL5 oligomerization is not required for the extravasation of adherent leukocytes.CCL5 is upregulated in breast cancer and promotes tumor progression through the attraction of proinflammatory macrophages in addition to its actions on tumor cells, stromal cells, and the vasculature.

Tumor protein p63 is a protein also known as transformation-related protein 63, TP63, and p63. Tumor protein p63 / p63 is a member of the p53 family of transcription factors whose members P53, p63, and p73 have similar features in their gene structures and functions. An animal model, p63-/- mice has been useful in difining the role p63 plays in the development and maintenance of stratified epithelial tissues. This p63 encoding protein p63 has a dramatic impact on replenishment of cutaneous epithelial stem cells and on ovarian germ cell survival. Although these two fundamental roles of p63 attest to its powerful place in development, its other functions, specifically the apparent capacity of p63, is to supervise the emergence of new cell populations in the breast, prostate, cervix, and upper reproductive tract. P63-/- mice have several development defects which include the lack of limbs and other tissues, such as teeth and mammary glands, which develop as a result of interactions between mesenchyme and epithelium. Mutations in this protein are associated with ectodermal dysplasia, and cleft lip / palate syndrome 3, ADULT syndrome (acro-dermato-ungual-lacrimal-tooth), limb-mammary syndrome, et al.

PDRG1, also known as C2orf126, belongs to the prefoldin subunit beta family. It is predominantly expressed in normal testis and exhibits reduced but detectable expression in other organs. PDRG1 may play a role in chaperone-mediated protein folding. PDRG1 is overexpressed in tumors relative to normal tissues. Its expression is upregulated in multiple malignancies including cancers of the colon, rectum, ovary, lung, stomach, breast and uterus when compared to their respective matched normal tissues. Thus PDRG1 is a high-value novel tumor marker that could play a role in cancer development and/or progression.

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

C-type lectin domain family 3 member A (CLEC3A) is a poorly characterized protein belonging to the superfamily of C-type lectins. Elevated CLEC3A expression may correlate with breast IDC metastatic potential and indicated a poor prognosis in breast IDC. CLEC3A knockdown inhibited BC cell growth and metastasis might be through suppressing PI3K/AKT signaling activity. That CLEC3A is a promising therapeutic target for BC in the future. Matrilysin (MMP-7) plays important roles in tumor progression. Previous studies have suggested that MMP-7 binds to tumor cell surface and promotes their metastatic potential. C-type lectin domain family 3 member A (CLEC3A) as a membrane-bound substrate of MMP-7. CLEC3A binds to heparan sulfate proteoglycans on cell surface, leading to the enhancement of cell adhesion to integrin ligands on ECM. It can be speculated that the cleavage of CLEC3A by MMP-7 weakens the stable adhesion of tumor cells to the matrix and promotes their migration in tumor microenvironments.

Monocyte chemoattractant protein 1 (MCP-1), also called CCL2, is a member of the beta (C-C) subfamily of chemokines that is a chemoattractant for monocytes and basophils but not eosinophils or neutrophils. CCL2 binds the cognate receptor CCR2, and together this signaling pair has been shown to have multiple pro-tumorigenic roles, from mediating tumor growth and angiogenesis to recruiting and usurping host stromal cells to support tumor progression. CCL2 is found in the circulation, where it has been suggested as a diagnostic biomarker of breast cancer and prostate cancer. CCL2 can also induce arachidonic acid release in human monocytes, which has been shown to be involved in adhesion and induction of the chemotactic response, in a pertussis-toxinsensitive manner.

Prolactin receptor (PRLR) is highly expressed in a subset of human breast cancer and prostate cancer, which makes it a potential target for cancer treatment. In clinical trials, the blockade of PRLR was shown to be safe but with poor efficacy. It is therefore urgent to develop new therapies against PRLR target. Bispecific antibodies (BsAbs) could guide immune cells toward tumor cells, and produced remarkable effects in some cancers. PRLR Protein, Cynomolgus, Recombinant (His) is expressed in HEK293 mammalian cells with C-His tag. The predicted molecular weight is 25.75 kDa and the accession number is A0A2K5WXK1.

Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC). Also regulates actin-myosin interaction through a non-kinase activity. Phosphorylates PTK2B/PYK2 and myosin light-chains. Involved in the inflammatory response (e.g. apoptosis, vascular permeability, leukocyte diapedesis), cell motility and morphology, airway hyperreactivity and other activities relevant to asthma. Required for tonic airway smooth muscle contraction that is necessary for physiological and asthmatic airway resistance. Necessary for gastrointestinal motility. Implicated in the regulation of endothelial as well as vascular permeability, probably via the regulation of cytoskeletal rearrangements. In the nervous system it has been shown to control the growth initiation of astrocytic processes in culture and to participate in transmitter release at synapses formed between cultured sympathetic ganglion cells. Critical participant in signaling sequences that result in fibroblast apoptosis. Plays a role in the regulation of epithelial cell survival. Required for epithelial wound healing, especially during actomyosin ring contraction during purse-string wound closure. Mediates RhoA-dependent membrane blebbing. Triggers TRPC5 channel activity in a calcium-dependent signaling, by inducing its subcellular localization at the plasma membrane. Promotes cell migration (including tumor cells) and tumor metastasis. PTK2B/PYK2 activation by phosphorylation mediates ITGB2 activation and is thus essential to trigger neutrophil transmigration during acute lung injury (ALI). May regulate optic nerve head astrocyte migration. Probably involved in mitotic cytoskeletal regulation. Regulates tight junction probably by modulating ZO-1 exchange in the perijunctional actomyosin ring. Mediates burn-induced microvascular barrier injury; triggers endothelial contraction in the development of microvascular hyperpermeability by phosphorylating MLC. Essential for intestinal barrier dysfunction. Mediates Giardia spp.-mediated reduced epithelial barrier function during giardiasis intestinal infection via reorganization of cytoskeletal F-actin and tight junctional ZO-1. Necessary for hypotonicity-induced Ca(2+) entry and subsequent activation of volume-sensitive organic osmolyte/anion channels (VSOAC) in cervical cancer cells. Responsible for high proliferative ability of breast cancer cells through anti-apoptosis.

Hypoxia up-regulated protein 1, also known as 15 kDa oxygen-regulated protein, 17 kDa glucose-regulated protein, ORP-15, GRP-17, and HYOU1, is a member of the heat shock protein 7 family. Seven members from four different heat shock protein (HSP) families were identified including HYOU1 (ORP15), HSPC1 (HSP86), HSPA5 (Bip), HSPD1 (HSP6), and several isoforms of the two testis-specific HSP7 chaperones HSPA2 and HSPA1L. HYOU1 is highly expressed in tissues that contain well-developed endoplasmic reticulum and synthesize large amounts of secretory proteins. It is highly expressed in the liver and pancreas. HYOU1 is also expressed in macrophages within aortic atherosclerotic plaques and in breast cancers. HYOU1 has a pivotal role in cytoprotective cellular mechanisms triggered by oxygen deprivation. It may play a role as a molecular chaperone and participate in protein folding. Suppression of HYOU1 is associated with accelerated apoptosis. It is suggested to have an important cytoprotective role in hypoxia-induced cellular perturbation. This protein is up-regulated in tumors, especially in breast tumors, and thus it is associated with tumor invasiveness.

Plexin domain-containing protein 1, also known as tumor endothelial marker 3, tumor endothelial marker 7 and PLXDC1 and TEM3, is a secreted, cytoplasm and single-pass type I membrane protein that belongs to the plexin family. PLXDC1 / TEM3 is detected in endothelial cells from colorectal cancer, and in endothelial cells from primary cancers of the lung, liver, pancreas, breast and brain. It is expressed in fibrovascular membrane with increased expression in individuals with proliferative diabetic retinopathy. PLXDC1 / TEM3 is not detectable in endothelial cells from normal tissue. PLXDC1 / TEM3 plays a critical role in endothelial cell capillary morphogenesis. PLXDC1 / TEM3 may play a significant role in the proliferation and maintenance of neovascular endothelial cells in the formation of fibrovascular membranes (FVMs). PLXDC1 / TEM3 may be a molecular target for new diagnostic and therapeutic strategies for proliferative diabetic retinopathy (PDR). PLXDC1 / TEM3 interacts with NID1. It may also interact with CTTN.

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. Macrophage Metalloelastase, also known as Matrix metalloproteinase-12, Macrophage elastase, MMP12, and MMP-12, is a secreted protein that belongs to the peptidase M1A family. MMP12 is a macrophage-secreted elastase that is highly induced in the liver and lung in response to S. mansoni eggs and contains four hemopexin-like domains. MMP12 is a proteolytic enzyme responsible for the cleavage of plasminogen to angiotensin, which has an angiostatic effect. It may be involved in tissue injury and remodeling and has significant elastolytic activity. It may be related to prognosis in breast cancer patients. MMP12 promotes fibrosis by limiting the expression of specific ECM-degrading MMPs. Like MMP12, MMP13 expression is highly dependent on IL-13 and type I I-IL-4 receptor signaling. MMP12 is a potent proinflammatory and oncogenic molecule. MMP12 up-regulation plays a critical role in emphysema to lung cancer transition that is facilitated by inflammation.

RRM1 is a subunit of ribonucleoside-diphosphate reductase which is constituted by two subunits. Ribonucleoside-diphosphate reductase is an enzyme essential for the production of deoxyribonucleotides prior to DNA synthesis in S phase of dividing cells. RRM1 is one of several genes located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. RRM1 may play a role in malignancies and disease that involve this region.

ARHI, also known as DIRAS3, belongs to the small GTPase superfamily, Di-Ras family. ARHI gene is a novel tumor suppressor gene located on chromosome 1p31. Downregulation of ARHI expression has been detected in many types of cancer. ARHI is expressed in normal ovarian and breast epithelial cells but not in ovarian and breast cancers. As a suppressor, ARHI is not only an important factor in the pathogenesis of gastric cancer, but also a potential factor for tumor aggravation. ARHI expression in gastric cancer can be employed to indicate favorable prognosis for the disease.

RAB1B, a member of the RAS oncogene family, was significantly down-regulated in highly metastatic breast cancer cells. Moreover, down-regulation of RAB1B was also found to promote the proliferation and migration of TNBC cells in vitro and in vivo. Mechanistically, loss of RAB1B resulted in elevated expression of TGF-beta receptor 1 (TbetaR1) through decreased degradation of ubiquitin, increased levels of phosphorylated SMAD3 and TGF-beta-induced epithelial-mesenchymal transition (EMT). Furthermore, low RAB1B expression correlated with poor prognosis in breast cancer patients.RAB1B acts as a metastasis suppressor in TNBC by regulating the TGF-beta/SMAD signaling pathway and RAB1B may serve as a novel biomarker of prognosis and the response to anti-tumor therapeutics for patients with TNBC.

Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) was identified as a metastatic driver. CEACAM5 overproduction enriched for an epithelial gene expression pattern and facilitated tumor outgrowth at metastatic sites. Tissues from patients with metastatic breast cancer confirmed elevated levels of CEACAM5 in lung metastases relative to breast tumors, and an inverse correlation between CEACAM5 and the mesenchymal marker vimentin was demonstrated.

ITGB1 (Integrin Subunit Beta 1) is a Protein Coding gene. This gene encodes a beta subunit, which is a type 1 transmembrane protein of the integrin beta chain family. ITGB1 is a heterodimeric cell-surface receptor involved in cell functions such as proliferation, migration, invasion, and survival. ITGB1 has been recognized to play a major role in tumor growth, invasion, and metastasis. Using luciferase assays, the researcher identified ITGB1 as a direct target of miR-134. ITGB1 is a direct target of miR-493-5p suggesting that ITGB1 and miR-493-5p may have potential prognostic value and may be useful as tumor biomarkers for the diagnosis of NSCLC patients. Diseases associated with ITGB1 include Gallbladder Cancer and Breast Cancer.

Protein arginine N-methyltransferase 6, also known as Histone-arginine N-methyltransferase PRMT6, PRMT6, and HRMT1L6, is a member of the protein arginine N-methyltransferase family and PRMT6 subfamily. PRMT6 is highly expressed in kidney and testes. PRMT6 is known to catalyze the generation of asymmetric dimethylarginine in polypeptides. It has been implicated in human immunodeficiency virus pathogenesis, DNA repair, and transcriptional regulation. PRMT6 is known to methylate histone H3 Arg-2 (H3R2), and this negatively regulates the lysine methylation of H3K4 resulting in gene repression. PRMT6 plays a key role in coupling process by functioning as a transcriptional coactivator that can regulate alternative splicing. PRMT6 coactivates the progesterone, glucocorticoid and oestrogen receptors in luciferase reporter assays in a hormone-dependent manner. Small interfering RNA (siRNA) oligonucleotide duplex knockdown of PRMT6 disrupts oestrogen-stimulated transcription of endogenous GREB1 and progesterone receptor in MCF-7 breast cancer cells. Neutralizing the activity of PRMT6 could inhibit tumor progression and may be of cancer therapeutic significance.

Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a tumor suppressor and a negative regulator of several receptor tyrosine kinases. Leucine-rich repeats and immunoglobulin-like domains containing protein 1 (LRIG1) is an endogenous feedback regulator of receptor tyrosine kinases (RTKs) and was recently shown to inhibit the growth of different types of malignancies. Leucine-rich repeats and immunoglobulin-like domains 1(LRIG1)is a kind of transmembrane glycoprotein, which is induced by epidermal growth factor (EGF) and develops inhibitory negative feedback by specific binding with epidermal growth factor receptor (EGFR). LRIG1 expression is broadly decreased in human cancer and breast cancer and low expression of LRIG1 has been linked to decreased relapse-free survival.

Chemokine (C-X-C motif) ligand 17 (CXCL17) is the latest member of the chemokine family. CXCL17 is a potential oncogene and promising therapeutic target, is an independent biomarker of poor prognosis in patients with breast cancer, and can promote proliferation and migration of breast cancer cells in vitro and in vivo. CXCL17 is expressed in a variety of cancers and promotes tumor progression by recruiting myeloid-derived suppressor cells (MDSCs). CXCL17 attenuates IMQ-induced psoriasis-like skin inflammation by recruiting MDSCs and Tregs, which may be important for regulating excessive inflammation in psoriasis skin. CXCL17 production correlated with adverse immune infiltration and might be an important target for anti-HCC therapies. CXCL17 is a major regulator of mucosal inflammatory responses.

Gamma-Synuclein (SNCG) is a member of the Synuclein protein family. Gamma-Synuclein is mostly expressed in the peripheral nervous system and retina. Gamma-Synuclein plays a role in neurofilament network integrity and may be involved in modulating axonal architecture during development and in the adult. In addition, it may also function in modulating the keratin network in skin. SNCG expression in breast tumors has been as a marker for tumor progression. SNCG is also believed to be involved in the pathogenesis of neurodegenerative diseases.

Ephrin-A1 is a member of the A-type ephrin family of cell surface proteins that function as ligands for the A-type Eph receptor tyrosine kinase family. Ephrin-A1 can be induced by TNF and IL1B. Its expression levels can be down-regulated in primary glioma tissues compared to the normal tissues. The soluble monomeric form is expressed in the glioblastoma multiforme (GBM) and breast cancer cells. Soluble Ephrin-A1 is necessary for the transformation of HeLa and SK-BR3 cells and participates in the relocalization of EPHA2 away from sites of cell-cell contact during transformation. Ephrin-A1 plays an important role in angiogenesis and tumor neovascularization.

Fatty Acid Binding Protein 3 (FABP3) is a small cytoplasmic protein (15 kDa) that is released from cardiac myocytes following an ischemic episode. Like the nine other distinct FABPs that have been identified, FABP3 is involved in active fatty acid metabolism where it transports fatty acids from the cell membrane to mitochondria for oxidation. FABPs are divided into at least three distinct types, namely the hepatic-, intestinal- and cardiac-types. They form 14-15 kDa proteins and are thought to participate in the uptake, intracellular metabolism and/or transport of long-chain fatty acids. They may also be responsible in the modulation of cell growth and proliferation. The FABP3 gene contains four exons and its function is to arrest growth of mammary epithelial cells. This gene is also a candidate tumor suppressor gene for human breast cancer. FABP3 is a sensitive biomarker for myocardial infarction and can be detected in the blood within one to three hours of onset of pain.

Tryptases are serine proteases with trypsin-like specificity. Together with chymases and Cathepsin G, tryptases are important players in mast cell mediation of inflammatory and allergic responses. Tryptase alpha/beta-1(TPSAB1), also known as mast cell protease 7 (MCPT7), it exhibits anticoagulant activity due to its ability to degrade fibrinogen in the presence of a diverse array of protease inhibitors in plasma. The two Isoform 1 and isoform 2 are expressed in lung, stomach, spleen, heart and skin; in these tissues, isoform 1 is predominant. Isoform 2 is expressed in aorta, spleen, and breast tumor, with highest levels in the endothelial cells of some blood vessels surrounding the aorta, as well as those surrounding the tumor and low levels, if any, in mast cells. Isoform 2 cleaves large substrates, such as fibronectin, more efficiently than isoform 1, but seems less efficient toward small substrates. It may play a role in innate immunity.

Tumor necrosis factor receptor superfamily member 27, also known as XEDAR and EDA2R, is a type III transmembrane protein of the TNFR superfamily. EDA2R consists of extracellular domain (ECD) with 3 cysteine-rich repeats and a single transmembrane domain but lacks an N-terminal signal peptide. EDA2R is widely expressed, notably in embryonic basal epidermal cells and maturing hair follicles. Even though it does not contain a cytoplasmic death domain, EDA2R can associate with Fas and induce EDA‑A2 dependent apoptosis. Its transcription is directly induced by p53, and it mediated cell death is p53 dependent. it is down‑regulated in breast, colon, and lung cancers, particularly in cases with p53 mutations. It also plays a role in EDA‑A2 induced skeletal muscle degeneration and osteoblast differentiation. Mutations in the EDA gene are associated with the X-linked form of Hypohidrotic Ectodermal Dysplasia (HED), a disease typically characterized by abnormal hair, teeth and sweat glands.

Prolactin receptor (PRLR) is highly expressed in a subset of human breast cancer and prostate cancer, which makes it a potential target for cancer treatment. In clinical trials, the blockade of PRLR was shown to be safe but with poor efficacy. It is therefore urgent to develop new therapies against PRLR target. Bispecific antibodies (BsAbs) could guide immune cells toward tumor cells, and produced remarkable effects in some cancers. PRLR Protein, Canine, Recombinant (hFc) is expressed in HEK293 mammalian cells with C-hFc tag. The predicted molecular weight is 53.89 kDa and the accession number is XM_038663941.1.

Protein S100-A7, also known as S100 calcium-binding protein A7, Psoriasin, S100A7, and PSOR1, is a secreted protein which belongs to theS-100 family. S100A7 was first isolated from skin involved by psoriasis, which can be induced in cultured squamous epithelial cells. S100A7 is expressed by both normal cultured and malignant keratinocytes and malignant breast epithelial cells within ductal carcinoma in situ, suggesting an association with abnormal pathways of differentiation. S100A7 plays a role in the pathogenesis of inflammatory skin disease, as a chemotactic factor for hematopoietic cells. It also plays a role in early stages of breast tumor progression in association with the development of the invasive phenotype.

Aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), also known as Aldehyde dehydrogenase 1 (ALDH1), or Retinaldehyde Dehydrogenase 1 (RALDH1), is an enzyme that is expressed at high levels in stem cells and that has been suggested to regulate stem cell function. The retinaldehyde dehydrogenase (RALDH) subfamily of ALDHs, composed of ALDH1A1, ALDH1A2, ALDH1A3, and ALDH8A1, regulate development by catalyzing retinoic acid biosynthesis. The ALDH1A1 protein belongs to the aldehyde dehydrogenases family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. ALDH1A1 also belongs to the group of corneal crystallins that help maintain the transparency of the cornea. Increased ALDH1A1 activity has been found in the stem cell populations of leukemia and some solid tumors. In tumor specimens, increased ALDH1A1 immunopositivity was found not only in secretory type cancer epithelial cells but also in neuroendocrine tumor populations. ALDH1 has been identified as a reliable marker of breast cancer stem cells. ALDH1 expression in primary cancer is an independent prognostic factor in node-positive breast cancer patients. ALDH1A1 plays a key role in normal hematopoiesis, and as a TLX1 transcriptional target, ALDH1A1 may contribute to the ability of this homeoprotein to alter cell fate and induce tumor growth.

AIM2, Absent In Melanoma 2 is a member of the interferon-inducible HIN-200 protein family that contains an amino-terminal pyrin domain and a carboxy-terminal oligonucleotide/oligosaccharide-binding domain, senses cytoplasmic DNA by means of its oligonucleotide/oligosaccharide-binding domain and interacts with ASC (apoptosis-associated speck-like protein containing a CARD) through its pyrin domain to activate caspase-1. In response to foreign cytoplasmic DNA, AIM2 forms an inflammasome, resulting in caspase activation in inflammatory cells. It had been pointed to a role of AIM2 function in both inflammation and cancer. AIM-2 antigen is expressed in a wide variety of tumor types, including neuroectodermal tumors, as well as breast, ovarian and colon carcinomas. AIM-2 could be used as a tumor antigen target for monitoring vaccine trials or to develop antigen specific active immunotherapy for glioma patients.

Koebnerisin is also known as protein S100-A7A (S100A7A), S100 calcium-binding protein A7-like 1 (S100A7L1) or S100 calcium-binding protein A15 (S100A15). Human S100A7A / S100A15 is a novel member of the S100 family of EF-hand calcium-binding proteins and was recently identified in psoriasis, where it is significantly upregulated in lesional skin. S100A7 is expressed by both normal cultured and malignant keratinocytes and malignant breast epithelial cells within ductal carcinoma in situ, suggesting an association with abnormal pathways of differentiation. S100A7 plays a role in the pathogenesis of inflammatory skin disease, as a chemotactic factor for hematopoietic cells. It also plays a role in early stages of breast tumor progression in association with the development of the invasive phenotype. The association of the 11.2 kDa S100A7A / S100A15 with psoriasis suggests that it contributes to the pathogenesis of the disease and could provide a molecular target for 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.

c-Abl belongs to the class of tyrosine kinases and is the prototype of a subfamily which includes two members, c-Abl and Arg (Abl-related gene). Both proteins are localized at the cell membrane, actin cytoskeleton and cytosol, and c-Abl is present in the nucleus as well. c-Abl is a non-receptor tyrosine kinase that participates in multiple signaling pathways linking the cell surface, cytoskeleton, and the nucleus. Recent in vitro studies have also linked c-Abl to amyloid-beta-induced toxicity and tau phosphorylation. c-Abl has been implicated in many cellular processes including differentiation, division, adhesion, death, and stress response. c-Abl is a latent tyrosine kinase that becomes activated in response to numerous extra- and intra-cellular stimuli. The c-Abl protein is a ubiquitously expressed nonreceptor tyrosine kinase involved in the development and function of many mammalian organ systems, including the immune system and bone. It regulates the cellular response to TAM through functional interaction with the estrogen receptor, which suggests c-Abl as a therapeutic target and a prognostic tumor marker for breast cancer. c-Abl also plays a key role in signaling chemokine-induced T-cell migration. In addition, c-Abl contains NLSs (nuclear localization signals) and DNA-binding sequences important for nuclear functions. c-Abl has become an important therapeutic target in human chronic myeloid leukaemia.Cancer ImmunotherapyImmune CheckpointImmunotherapyTargeted Therapy

Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Regulates phosphorylation of ITPR3 and plays a role in the regulation of calcium homeostasis at the endoplasmic reticulum. Regulates RB1 phosphorylation and activity. Acts as both a negative regulator of PPARGC1A acetylation and a potent activator of PPAR signaling and fatty acid oxidation. Regulates translation of HIF1A by sequestering MTOR, and thereby plays a role in neoangiogenesis and tumor vascularization. Regulates PER2 nuclear localization and circadian function. Cytoplasmic PML is involved in the regulation of the TGF-beta signaling pathway. Required for normal development of the brain cortex during embryogenesis. Plays a role in granulopoiesis or monopoiesis of myeloid progenitor cells. May play a role regulating stem and progenitor cell fate in tissues as diverse as blood, brain and breast. Shows antiviral activity towards lymphocytic choriomeningitis virus (LCMV) and the vesicular stomatitis virus (VSV).

Insulin-like growth factor 2 (IGF-2/IGF-II) is a member of the insulin family of polypeptide growth factors, which are involved in development and growth. It is an imprinted gene, expressed only from the paternal allele, and epigenetic changes at this locus are associated with Wilms tumor, Beckwith-Wiedemann syndrome, rhabdomyosarcoma, and Silver-Russell syndrome. IGF-2/IGF-II is a mediator of prolactin-induced alveologenesis; prolactin, IGF-2, and cyclin D1, all of which are overexpressed in breast cancers, are components of a developmental pathway in the mammary gland. IGF-2 and exhibited statistically significant, positive associations with colorectal cancer risk when cases were confined to those diagnosed within a relatively short period after enrolment. Circulating IGF-2 and IGFBP-3 can serve as early indicators of impending colorectal cancer. IGF-2/IGF-II appears to be involved in the progression of many tumors. It binds to at least two different types of receptors: IGF type 1 (IGF 1R) and mannose 6-phosphate/IGF type 2 (M6-P/IGF 2R). Ligand binding to IGF 1R provokes mitogenic and anti-apoptotic effects. M6-P/IGF 2R has a tumor suppressor function—it mediates IGF 2 degradation. Mutation of M6-P/IGF 2R causes both diminished growth suppression and augmented growth stimulation. This study aimed to investigate the role of IGF 2 and its receptors (IGF 1R and IGF 2R) in human gastric cancer.

Calmodulin-like protein 3 (CALML3) is similar to that of authentic calmodulin and may actually compete with calmodulin by binding, with different affinity, to cellular substrates. Calmodulin-like protein 3 (CALML3) is a tumor-sensitive protein specifically expressed in normal epithelial cells but downregulated in tumorigenesis. Downregulation of the protein is an early event in breast cancer development. One of the most pressing questions raised by the discovery of CLP/CALML3 is that of its potential targets. Although it is 85% identical to human calmodulin, the distinct properties of CLP suggest that it has specific targets or targets that only partially overlap with those of calmodulin. Research has identified the unconventional myosin-10 (Myo10) as a specific target of CALML3. The discovery of Myo10 as a specific target of CALML3 is highly significant and suggests multiple lines of further research such as investigations of the Ca2+ regulation of Myo10 and the role of the loss of CLP in epithelial differentiation, adhesion, and cancer. Cells expressing CALML3 displayed a striking increase in the number and length of myosin-10-positive filopodia and showed increased mobility in a wound healing assay.

Fragile histidine triad, also known as FHIT, may play a key role in differentiating humans from apes. Fragile histidine triad gene belongs to the histidine triad gene family. It has been shown that fragile histidine triad synergizes with VHL, another tumor suppressor, in protecting against chemically - induced lung cancer. Fragile histidine triad gene works as a tumor suppressor as it has been demonstrated in animal studies. The exact molecular function of FHIT is still partially unclear. It also acts as a tumor suppressor of HER2/neu driven breast cancer.