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Adipose-derived stem cells (ADSCs) play a vital role in colorectal cancer (CRC) progression, but the mechanism remains largely unknown. Herein, we found that ADSCs isolated from CRC patients produced more cysteine-rich 61 (Cyr61) than those from healthy donors, and the elevated serum Cyr61 levels were associated with advanced TNM stages. Moreover, serum Cyr61 displayed a better diagnostic value for CRC compared to carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9). Mechanistically, integrin αV β5 was identified as the func