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.

中文翻译：

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纤连蛋白通过大肠癌中CDC42-YAP依赖性信号通路促进肿瘤细胞生长和耐药性。

纤连蛋白（FN）是细胞外基质（ECM）的一种高分子量糖蛋白，可与跨膜受体蛋白或ECM中的其他元素结合。FN的表达可能参与癌细胞的增殖或迁移，并开始阐明导致FN诱导的肿瘤信号的分子机制。在这里，我们报道了在结直肠癌患者的那些化学耐药性肿瘤组织中观察到FN的表达升高。一致地，FN培养物显着增强了结肠直肠癌细胞的增殖，在体外和体内诱导了结肠直肠肿瘤的持续生长和耐药性。在机制上，FN可能与整联蛋白αvβ1结合，导致下游细胞分裂周期42 / yes相关蛋白1（CDC42 / YAP-1）信号通路激活。CDC42 / YAP-1信号的激活诱导转录因子SOX2的上调，从而导致结直肠癌的持续生长和耐药性。整联蛋白αvβ1的阻断显着抑制了结直肠癌的生长和体内外耐药性的发展，为临床结直肠癌的治疗提供了新的靶点。