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

Discover oncology 2026 Vol.17(1)

Lu P, Zheng C, Zhang J, Zhu X, Chen X, Zhang J, Cao Y, Huang Z

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[BACKGROUND] Oxaliplatin (OXA) resistance poses a significant challenge to the efficacy of chemotherapy for advanced colorectal cancer (CRC).

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APA Lu P, Zheng C, et al. (2026). Oxaliplatin upregulates Cyr61 expression by inhibiting the Hippo-YAP pathway which contributes to drug resistance of colorectal cancer cells.. Discover oncology, 17(1). https://doi.org/10.1007/s12672-026-04530-2
MLA Lu P, et al.. "Oxaliplatin upregulates Cyr61 expression by inhibiting the Hippo-YAP pathway which contributes to drug resistance of colorectal cancer cells.." Discover oncology, vol. 17, no. 1, 2026.
PMID 41606217

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.

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