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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using a data mining approach for the discovery of new targets for antibody therapy of colon cancer, we identified MS4A12, a sequence homologue of CD20. We show that MS4A12 is a cell surface protein. Expression analysis and immunohistochemistry revealed MS4A12 to be a colonic epithelial cell lineage gene confined to the apical membrane of colonocytes with strict transcriptional repression in all other normal tissue types. Expression is maintained upon malignant transformation in 63% of colon cancers. Ca(2+) flux analyses disclosed that MS4A12 is a novel component of store-operated Ca(2+) entry in intestinal cells. Using RNAi-mediated gene silencing, we show that loss of MS4A12 in LoVo colon cancer cells attenuates epidermal growth factor receptor-mediated effects. In particular, proliferation, cell motility, and chemotactic invasion of cells are significantly impaired. Cancer cells expressing MS4A12, in contrast, are sensitized and respond to lower concentrations of epidermal growth factor. In summary, these findings have implications for both the physiology of colonic epithelium as well as for the biology and treatment of colon cancer.
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PMID:MS4A12 is a colon-selective store-operated calcium channel promoting malignant cell processes. 1845 Nov 74

Colon cancer-associated MS4A12 is a novel colon-specific component of store-operated Ca2+ (SOC) entry sensitizing cells for epidermal growth factor (EGF)-mediated effects on proliferation and chemotaxis. In the present study, we investigated regulation of the MS4A12 promoter to understand the mechanisms responsible for strict transcriptional restriction of this gene to the colonic epithelial cell lineage. DNA-binding assays and luciferase reporter assays showed that MS4A12 promoter activity is governed by a single CDX homeobox transcription factor binding element. RNA interference (RNAi)-mediated silencing of intestine-specific transcription factors CDX1 and CDX2 and chromatin immunoprecipitation (ChIP) in LoVo and SW48 colon cancer cells revealed that MS4A12 transcript and protein expression is essentially dependent on the presence of endogenous CDX2. In summary, our findings provide a rationale for colon-specific expression of MS4A12. Moreover, this is the first report establishing CDX2 as transactivator of tumor growth-promoting gene expression in colon cancer, adding to untangle the complex and conflicting biological functions of CDX2 in colon cancer and supporting MS4A12 as important factor for normal colonic development as well as for the biology and treatment of colon cancer.
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PMID:Selective activation of tumor growth-promoting Ca2+ channel MS4A12 in colon cancer by caudal type homeobox transcription factor CDX2. 1978 Oct 65

Cancer is often viewed as a caricature of normal developmental processes, but the extent to which its cellular heterogeneity truly recapitulates multilineage differentiation processes of normal tissues remains unknown. Here we implement single-cell PCR gene-expression analysis to dissect the cellular composition of primary human normal colon and colon cancer epithelia. We show that human colon cancer tissues contain distinct cell populations whose transcriptional identities mirror those of the different cellular lineages of normal colon. By creating monoclonal tumor xenografts from injection of a single (n = 1) cell, we demonstrate that the transcriptional diversity of cancer tissues is largely explained by in vivo multilineage differentiation and not only by clonal genetic heterogeneity. Finally, we show that the different gene-expression programs linked to multilineage differentiation are strongly associated with patient survival. We develop two-gene classifier systems (KRT20 versus CA1, MS4A12, CD177, SLC26A3) that predict clinical outcomes with hazard ratios superior to those of pathological grade and comparable to those of microarray-derived multigene expression signatures.
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PMID:Single-cell dissection of transcriptional heterogeneity in human colon tumors. 2249 Jun 19

Lack of normal differentiation was considered as a common defect in cancer cells. MS4A12, a colon-specific gene, belongs to MS4A family that plays an important role in differentiation, proliferation and cell cycle regulation. The aim of the study was to investigate MS4A12 role in colon cancer cell differentiation and its prognostic value in colon cancer. We used sodium butyrate (BS) to set up differentiated model of colon cancer cell line LoVo. Cell differentiation was evaluated with ALP activity and E-cadherin. We used BS (4 mmol/L) inducing differentiation of LoVo cell and found after BS treated over 48h MS4A12 variant-1 (one of MS4A12 gene transcripts) as well as ALP and E-cadherin of LoVo cells were all increased significantly. When silence MS4A12 variant-1, the elevation of ALP and E-cadherin in BS-treated cells were all inhibited. Besides, after silence MS4A12 variant-1, the cells showed significant resistances to BS function of induction cell cycle arrest and apoptosis. Survival analysis used GEO datasets GSE39582 and GSE38832 that include 681 distinct colon cancer samples. Log-rank test and Cox's proportional hazards regression were applied to analyzing single and multiple prognostic variables, respectively. In early stage colon cancer, the patients with low MS4A12 expression had a poor survival (HR=1.72; p=0.036), while in advanced stage colon cancer MS412 had little prognostic value (HR=0.89; p=0.601). These results indicated MS4A12 might relate to colon cancer cell differentiation and supposed to be a risk classification marker for early stage colon cancer.
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PMID:Decreased expression of MS4A12 inhibits differentiation and predicts early stage survival in colon cancer. 2788 Oct 6