TFF2-CXCR4 Axis Is Associated with BRAF V600E Colon Cancer.
TFF2-CXCR4 Axis Is Associated with BRAF V600E Colon Cancer.
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DOI：
10.1158/1940-6207.capr-14-0444
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发表时间：
2015-07
期刊：
影响因子：
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通讯作者：
Chan AT
中科院分区：
文献类型：
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作者：
Gala MK;Austin T;Ogino S;Chan AT
Oncogene-induced senescence (OIS), a tumor suppressive mechanism that is induced by the replicative and metabolic stress of oncogene activation, is a key barrier in the development of BRAF V600E colon cancer. Inhibition of this mechanism has been observed through epigenetic changes observed in sporadic serrated polyps, as well as through the germline mutations associated with those who develop serrated polyposis. We hypothesize upregulated autocrine factors exist that are specific to the serrated pathway and also promote bypass of oncogene-induced senescence. To identify such autocrine factors, we integrate analyses of microarrays of sessile serrated polyps and two large colon cancer cohorts, the Cancer Genome Atlas (TCGA) (n = 153) and French national Cartes d’Identité des Tumeurs (CIT) program (n = 462), with enhanced gene annotation through natural language processing techniques of the existing medical corpus. We reproducibly associate higher expression of the ligand-receptor axis of TFF2 and CXCR4 with BRAF V600E mutant colon cancer (P = 3.0 × 10−3 and 0.077, respectively for TCGA; P = 3.0 × 10−8 and 5.1 × 10−7 for CIT). Given well-described oncogenic roles of TFF2 and CXCR4 in colon cancer, and availability of CXCR4 inhibitors for other clinical indications, this ligand-receptor axis may represent an actionable target for prevention and treatment of this molecular subtype of colorectal cancer.
