Abstract

The cytotoxic effect of 5-fluorouracil (5FU) and regorafenib (RF), drugs with different mechanisms of action used to treat colorectal cancer, on an HT29 cell line cultured on plastic or laminin 521 (LM-521) has been studied. It is first shown that LM-521 can increase the sensitivity of tumor cells to 5FU. A possible mechanism of the observed effect of LM-521 on the HT29 cell viability is proposed based on transcriptome and proteome analysis. The interaction of β1-containing integrins on the cell surface with LM-521 can activate the FAK/PI3K/Akt signaling pathways and promote phosphorylation of the YAP transcription coactivator and its binding to the complex with the 14-3-3σ protein. The formation of this complex leads to YAP retention in the cytoplasm and prevents its transport to the nucleus and the activation of antiapoptotic gene transcription.

中文翻译：

---

层粘连蛋白521调节5-氟尿嘧啶对HT29大肠癌细胞的杀伤作用

摘要

研究了5-氟尿嘧啶（5FU）和瑞戈非尼（RF）（用于治疗大肠癌的具有不同作用机制的药物）对在塑料或层粘连蛋白521（LM-521）上培养的HT29细胞系的细胞毒性作用。首先表明，LM-521可以增加肿瘤细胞对5FU的敏感性。基于转录组和蛋白质组分析，提出了观察到的LM-521对HT29细胞活力影响的可能机制。细胞表面上含有β1的整合素与LM-521的相互作用可以激活FAK / PI3K / Akt信号通路，并促进YAP转录共激活因子的磷酸化及其与14-3-3σ蛋白的复合物的结合。这种复合物的形成导致YAP保留在细胞质中，并阻止其转运到细胞核和激活抗凋亡基因转录。