A positive feedback loop of β-catenin/CCR2 axis promotes regorafenib resistance in colorectal cancer.

ABSTRACT: Resistance to molecular targeted therapies is a significant challenge for advanced colorectal cancer (CRC). Understanding the underlying mechanisms and developing effective strategies against regorafenib resistance are highly desired in the clinic. Here, we screened the expression of chemokine receptors and identified CC chemokine receptor 2 (CCR2) as a top upregulated gene in regorafenib-resistant cells. CCR2 silencing alleviated drug tolerance in regorafenib-resistant cells, while overexpression of CCR2 enhanced CRC cells resistance to regorafenib. Moreover, CCR2-mediated regorafenib tolerance was demonstrated to be associated with AKT/GSK3β-regulated β-catenin stabilization. In turn, β-catenin modulation is sufficient to trigger the transcriptional activation of CCR2 expression. Clinica

SUBMITTER: Ou B 

PROVIDER: S-EPMC6733926 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature