文章：

TMTC1通过整合素β1和β4促进卵巢癌细胞的侵袭能力

TMTC1 promotes invasiveness of ovarian cancer cells through integrins β1 and β4 

原文发布日期：2023-05-23 

英文摘要：

Ovarian cancer is the most lethal gynecological malignancy and is characterized by peritoneal disseminated metastasis. Although O-mannosyltransferase TMTC1 is highly expressed by ovarian cancer, its pathophysiological role in ovarian cancer remains unclear. Here, immunohistochemistry showed that TMTC1 was overexpressed in ovarian cancer tissues compared with adjacent normal ovarian tissues, and high TMTC1 expression was associated with poor prognosis in patients with ovarian cancer. Silencing TMTC1 reduced ovarian cancer cell viability, migration, and invasion in vitro, as well as suppressed peritoneal tumor growth and metastasis in vivo. Moreover, TMTC1 knockdown reduced cell-laminin adhesion, which was associated with the decreased phosphorylation of FAK at pY397. Conversely, TMTC1 overexpression promoted these malignant properties in ovarian cancer cells. Glycoproteomic analysis and Concanavalin A (ConA) pull-down assays showed that integrins β1 and β4 were novel O-mannosylated protein substrates of TMTC1. Furthermore, TMTC1-mediated cell migration and invasion were significantly reversed by siRNA-mediated knockdown of integrin β1 or β4. Collectively, these results suggest that TMTC1-mediated invasive behaviors are primarily through integrins β1 and β4 and that TMTC1 is a potential therapeutic target for ovarian cancer. 

摘要翻译： 

卵巢癌是最致命的妇科恶性肿瘤，其特点是腹膜播散性转移。尽管O-甘露糖基转移酶TMTC1在卵巢癌中高表达，但其在卵巢癌中的病理生理作用尚不明确。本研究通过免疫组化分析发现，与癌旁正常卵巢组织相比，TMTC1在卵巢癌组织中过度表达，且高表达TMTC1与患者不良预后相关。沉默TMTC1可降低卵巢癌细胞体外活力、迁移和侵袭能力，并抑制体内腹膜肿瘤生长和转移。此外，敲低TMTC1会减弱细胞与层粘连蛋白的粘附能力，这与FAK pY397位点磷酸化水平降低相关。相反，过表达TMTC1则能增强卵巢癌细胞的这些恶性特性。糖蛋白质组学分析和伴刀豆球蛋白A（ConA）下拉实验表明，整合素β1和β4是TMTC1的新型O-甘露糖基化蛋白底物。更重要的是，通过siRNA敲低整合素β1或β4能显著逆转TMTC1介导的细胞迁移和侵袭行为。综上所述，这些结果表明TMTC1主要通过整合素β1和β4介导侵袭行为，是卵巢癌潜在的治疗靶点。

原文链接：

TMTC1 promotes invasiveness of ovarian cancer cells through integrins β1 and β4