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- Title
Fibronectin promotes tumor cells growth and drugs resistance through a CDC42‐YAP‐dependent signaling pathway in colorectal cancer.
- Authors
Ye, Yu; Zhang, Ruifeng; Feng, Haiyang
- 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 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.
- Subjects
DRUG resistance in cancer cells; FIBRONECTINS; COLORECTAL cancer; CANCER cell proliferation; CANCER cell migration; EXTRACELLULAR matrix
- Publication
Cell Biology International, 2020, Vol 44, Issue 9, p1840
- ISSN
1065-6995
- Publication type
Article
- DOI
10.1002/cbin.11390