Abstract：
FYCO1, an autophagy adaptor, plays an essential role in the trafficking toward the plus-end of microtubules and the fusion of autophagosomes. Autophagic dysfunction is involved in numerous disease states, including cancers. Previous studies have implicated FYCO1 as one of the critical genes involved in the adenoma to carcinoma transition, but the biological function and mechanism of FYCO1 in carcinogenesis remain unclear. This study aims to elucidate the role and mechanism of up- and downregulation of FYCO1 in mediating tumor effects in HeLa cells. Functionally, FYCO1 promotes cellular migration, invasion, epithelial-mesenchymal transition, invadopodia formation, and matrix degradation, which are detected through wound healing, transwell, immunofluorescence, and Western blot approaches. Interestingly, the data show that although FYCO1 does not affect HeLa cell proliferation, cell cycle distribution, nor vessels\' formation, FYCO1 can block the apoptotic function. FYCO1 inhibits cleavage of PARP, caspase3, and caspase9 and increases Bcl-2/Bax ratio. Then, we used CK666, an Arp2/3 specific inhibitor, to confirm that FYCO1 may promote the migration and invasion of HeLa cells through the CDC42/N-WASP/Arp2/3 signaling pathway. Taken together, these results provide a new insight that FYCO1, an autophagy adaptor, may also be a new regulator of tumor metastasis.
摘要：
FYCO1，自噬适配器，在微管正端的运输和自噬体的融合中起着至关重要的作用。自噬功能障碍涉及许多疾病状态，包括癌症。以前的研究表明FYCO1是参与腺瘤向癌转变的关键基因之一，但FYCO1在癌变过程中的生物学功能和机制尚不清楚。本研究旨在阐明FYCO1上调和下调在HeLa细胞中介导肿瘤效应的作用和机制。功能上,FYCO1促进细胞迁移，入侵,上皮-间质转化，invadopodia形成，和基质退化，通过伤口愈合来检测，transwell,免疫荧光，和蛋白质印迹方法。有趣的是,数据显示，尽管FYCO1不影响HeLa细胞增殖，细胞周期分布，也不是血管编队，FYCO1可以阻断凋亡功能。FYCO1抑制PARP的裂解，caspase3和caspase9增加Bcl-2/Bax比值。然后，我们使用了CK666，一种Arp2/3特异性抑制剂，证实FYCO1可能通过CDC42/N-WASP/Arp2/3信号通路促进HeLa细胞的迁移和侵袭。一起来看,这些结果提供了一个新的见解，即自噬适配器FYCO1，也可能是肿瘤转移的新调控因子。
