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Fibronectin promotes tumor cells growth and drugs resistance through a CDC42‐YAP‐dependent signaling pathway in colorectal cancer
Author(s) -
Ye Yu,
Zhang Ruifeng,
Feng Haiyang
Publication year - 2020
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.11390
Subject(s) - colorectal cancer , cdc42 , cancer research , fibronectin , mouse model of colorectal and intestinal cancer , integrin , signal transduction , cell growth , downregulation and upregulation , cancer , biology , extracellular matrix , microbiology and biotechnology , medicine , receptor , biochemistry , gene
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 protumor signals begin to be elucidated. Here, we report that the elevated expression of FN was observed in those chemoresistant tumor tissues from patients with colorectal cancer. 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 cell division cycle 42/yes‐associated protein 1 (CDC42/YAP‐1) signaling pathway activation. The activation of CDC42/YAP‐1 signal induces the upregulation 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 a new target for clinical colorectal cancer treatment.