Fibronectin promotes tumor cells growth and drugs resistance through a CDC42-YAP dependent signaling pathway in colorectal cancer

Colorectal Cancer
22/05/2020

Ye Y, et al. Cell Biol Int 2020.

ABSTRACT

Fibronectin (FN) is a high-molecular weight glycoprotein of the extracellular matrix (ECM) that binds to membrane-spanning receptor proteins or other elements in ECM. The expression of FN could be involved in the cancer cells proliferation or migration, and the molecular mechanisms responsible for FN induced pro-tumor signals begin to be elucidated. Here we report that the elevated expression of FN was observed in those chemo-resistant tumor tissues from colorectal cancer patients. Consistently,


FN culture significantly strengthened the proliferation of colorectal cancer cells, induced the colorectal tumor sustained growth and drug resistance in vitro and in vivo. In mechanism, FN could bind to integrin αvβ1, resulting the downstream CDC42/YAP-1signaling pathway activation. The activation of CDC42/YAP-1signal induces the up-regulation of transcription factor SOX2, causing the sustained growth and drugs resistance in colorectal cancer. Blockade of integrin αvβ1 significantly suppressed the colorectal cancer growth and drugs resistance development in vitro and in vivo, which provides new target for clinical colorectal cancer treatment. This article is protected by copyright. All rights reserved.