Oxaliplatin upregulates Cyr61 expression by inhibiting the Hippo-YAP pathway which contributes to drug resistance of colorectal cancer cells.

ABSTRACT:

Background

Oxaliplatin (OXA) resistance poses a significant challenge to the efficacy of chemotherapy for advanced colorectal cancer (CRC). This study aimed to elucidate the role of OXA in regulating Cysteine-rich protein 61 (Cyr61) expression via the Hippo-Yes-associated protein (YAP) pathway in the context of chemotherapy-induced drug resistance.

Methods

We used Cell Counting Kit-8 to detect cell viability and proliferation. Expression of Cyr61 was determined by quantitative real-time PCR, western blotting (WB) and Enzyme-linked immunosorbent assay in CRC cell lines. The mechanism of OXA in regulating Cyr61 expression was studied by WB and co-immunoprecipitation.

Results

The results revealed that exposure to varying concentrations of OXA for 24 h induced increased mRNA and protein levels of Cyr61 in HCT8 and HCT116 CRC cells. Mechanistically, OXA-mediated overexpression of Cyr61 in CRC cells was attributed to inhibition of the Hippo-YAP pathway.

Conclusions

These findings provide novel insights into the mechanisms underlying chemotherapy-induced drug resistance in CRC and highlight the release of Cyr61 by CRC cells as a potential therapeutic target for overcoming OXA resistance in CRC.

SUBMITTER: Lu P 

PROVIDER: S-EPMC12923716 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature