Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Hippo pathway restricts the activity of transcriptional coactivators TAZ (WWTR1) and YAP. TAZ and YAP are reported to be overexpressed in various cancers, however, their prognostic significance in colorectal cancers remains unstudied. The expression levels of TAZ and YAP, and their downstream transcriptional targets, AXL and CTGF, were extracted from two independent colon cancer patient datasets available in the Gene Expression Omnibus database, totaling 522 patients. We found that mRNA expressions of both TAZ and YAP were positively correlated with those of AXL and CTGF (p<0.05). High level mRNA expression of TAZ, AXL or CTGF significantly correlated with shorter survival. Importantly, patients co-overexpressing all 3 genes had a significantly shorter survival time, and combinatorial expression of these 3 genes was an independent predictor for survival. The downstream target genes for TAZ-AXL-CTGF overexpression were identified by Java application MyStats. Interestingly, genes that are associated with colon cancer progression (ANTXR1, EFEMP2, SULF1, TAGLN, VCAN, ZEB1 and ZEB2) were upregulated in patients co-overexpressing TAZ-AXL-CTGF. This TAZ-AXL-CTGF gene expression signature (GES) was then applied to Connectivity Map to identify small molecules that could potentially be utilized to reverse this GES. Of the top 20 small molecules identified by connectivity map, amiloride (a potassium sparing diuretic), and tretinoin (all-trans retinoic acid) have shown therapeutic promise in inhibition of colon cancer cell growth. Using MyStats, we found that low level expression of either ANO1 or SQLE were associated with a better prognosis in patients who co-overexpressed TAZ-AXL-CTGF, and that ANO1 was an independent predictor of survival together with TAZ-AXL-CTGF. Finally, we confirmed that TAZ regulates Axl, and plays an important role in clonogenicity and non-adherent growth in vitro and tumor formation in vivo. These data suggest that TAZ could be a therapeutic target for the treatment of colon cancer.
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PMID:TAZ expression as a prognostic indicator in colorectal cancer. 2337 86

EFEMP2 is an extracellular matrix (ECM) glycoprotein that is a pivotal oncogene in tumor progression and metastasis. However, the function of EFEMP2 in colon cancer remains unknown. In this study, we found that EFEMP2 was highly expressed in colon cancer cells. Knockdown of EFEMP2 suppressed the growth and invasion of colon cancer LoVo and SW620 cells. Moreover, knockdown of EFEMP2 attenuated ERK1/2 activation, as well as decreased MMP-3 expression. Taken together, our study demonstrates that EFEMP2 is significantly expressed in colon cancer cells. EFEMP2 can promote the growth and invasion of colon cancer cells, possibly by regulation of ERK1/2 activation and MMP-3 expression. Therapies targeting EFEMP2 may be an effective strategy for treatment of colon cancer.
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PMID:EFEMP2 promotes colon cancer cell invasion and growth through the ERK1/2 signaling pathway. 3193 93