GSE146944 The role of HOXC6 in pancreatic adenocarcinoma (PDAC) progression.

Series Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers that lack effective therapeutic options. Here we show that the transcription factor Homeobox C6 (HOXC6) is overexpressed in PDAC and its inhibition blocks PDAC tumor growth and metastasis. By analyzing the HOXC6 shRNA expressing PDAC cells by RNA-sequencing, we identified PPP2R2B and MSK1 as key downstream mediators of HOXC6 function in PDAC. HOXC6 represses PPP2R2B to activate mTOR pathway in PDAC, which in part is necessary for HOXC6-loss induced PDAC inhibition. Additionally, HOXC6 expression is required for MSK1 expression and ectopic expression of MSK1 in HOXC6 knockdown cells rescues PDAC growth. RNA-seq analysis shows that MSK1 stimulates cancer promoting gene signature in PDAC. Pharmacological inhibition of MSK1 alone or in combination with mTOR inhibitors (rapamycin or everolimus) attenuate PDAC tumor growth. Therefore, these studies provide rationale for targeting HOXC6 transcriptional pathway to treat PDAC by inhibiting MSK1 and mTOR pathways.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research