J Cancer 2021; 12(7):1952-1959. doi:10.7150/jca.48891

Research Paper

Cyr61 mediates oxaliplatin resistance in colorectal cancer cells by regulating Bcl-xL expression

Yanfang Song1#, Yanli Kang3#, Zhen Lin2, Menglu Zeng2, Pengchong Shi2, Jia Lin1, Pingxia Lu2, Li Luo1, Yingping Cao2✉, Xianjin Zhu2✉

1. Department of Clinical Laboratory, Affiliated People Hospital of Fujian University of Traditional Chinese Medicine, 602 Bayiqi Road, Fuzhou, Fujian 350001, China.
2. Department of Clinical Laboratory, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian 350001, China.
3. Department of Clinical Laboratory, Fujian Provincial Hospital, 134 Dongjie Road, Fuzhou, Fujian 350001, China.
#These two authors contributed equally to this work.

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Citation:
Song Y, Kang Y, Lin Z, Zeng M, Shi P, Lin J, Lu P, Luo L, Cao Y, Zhu X. Cyr61 mediates oxaliplatin resistance in colorectal cancer cells by regulating Bcl-xL expression. J Cancer 2021; 12(7):1952-1959. doi:10.7150/jca.48891. Available from https://www.jcancer.org/v12p1952.htm

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Abstract

Although the clinical application of oxaliplatin (L-OHP) has improved the survival of colorectal cancer (CRC) patients, approximately half of patients with CRC fail to achieve good clinical outcomes, indicating resistance to L-OHP therapy. Cysteine-rich protein 61 (Cyr61), a multifunctional extracellular matrix protein, is highly expressed in a variety of tumors; increased Cyr61 expression is known to be closely involved in the chemotherapeutic resistance of many tumors, but its role in the L-OHP resistance of CRC cells has not been studied. In this study, we aimed to investigate the role of Cyr61 in the L-OHP resistance of CRC cells and examine the underlying mechanism. Our findings showed that the mRNA and protein levels of Cyr61 in L-OHP-resistant cells were significantly increased compared with those in nonresistant cells. Knockdown of Cyr61 enhanced the chemosensitivity of L-OHP-resistant cells to L-OHP. Mechanistically, we found that overexpression of Cyr61 decreased L-OHP-induced apoptosis in drug-resistant CRC cells through the regulation of Bcl-xL. Collectively, our results revealed for the first time that Cyr61 plays a crucial role in the resistance of CRC cells to L-OHP and indicated that targeting Cyr61 may be a promising therapeutic strategy to overcome L-OHP resistance in CRC.

Keywords: cysteine-rich protein 61, colorectal cancer, oxaliplatin, resistance