Blocking endothelin-1-receptor/β-catenin circuit sensitizes to chemotherapy in colorectal cancer.

ABSTRACT: The limited clinical response to conventional chemotherapeutics observed in colorectal cancer (CRC) may be related to the connections between the hyperactivated β-catenin signaling and other pathways in CRC stem-like cells (CRC-SC). Here, we show the mechanistic link between the endothelin-1 (ET-1)/ET-1 receptor (ET-1R) signaling and β-catenin pathway through the specific interaction with the signal transducer β-arrestin1 (β-arr1), which initiates signaling cascades as part of the signaling complex. Using a panel of patient-derived CRC-SC, we show that these cells secrete ET-1 and express ET_AR and β-arr1, and that the activation of ET_AR/β-arr1 axis promotes the cross-talk with β-catenin signaling to sustain stemness, epithelial-to-mesenchymal transition (EMT) phenotyp

SUBMITTER: Cianfrocca R 

PROVIDER: S-EPMC5596423 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature