Table_1_TBC1D2 Promotes Ovarian Cancer Metastasis via Inducing E-Cadherin Degradation.xlsx

BackgroundOvarian cancer (OC) is the most lethal gynecological malignancy worldwide. Increasing evidence indicates that TBC domain family is implicated in various cellular events contributing to initiation and development of different cancers, including OC. However, the role of TBC1D2, a crucial member of TBC domain family, remains unclear in OC.
MethodsIHC and qRT-PCR were employed to determine TBC1D2 expression in OC tissues and cells. In vitro and in vivo assays involving proliferation, migration, invasion were performed to explore the role of TBC1D2 in OC development. The underlying mechanism by which TBC1D2 promotes OC metastasis were elucidated using bioinformatics analysis, western blotting and co-immunoprecipitation.
ResultsUpregulation of TBC1D2 was found in OC and was associated with a poor prognosis. Meanwhile, TBC1D2 promoted OC cell proliferation, migration, and invasion in vitro and facilitated tumor growth and metastasis in vivo. Moreover, TBC1D2 contributed to OC cell invasion by E-cadherin degradation via disassembling Rac1-IQGAP1 complex. In addition, miR-373-3p was screened out and identified to inhibit OVCAR3 invasion via negative regulation of TBC1D2.
ConclusionOur findings indicated that TBC1D2 is overexpressed in OC and contributes to tumor metastasis via E-cadherin degradation. This study suggests that TBC1D2 may be an underlying therapeutic target for OC.

背景：卵巢癌（Ovarian cancer, OC）是全球致死率最高的妇科恶性肿瘤。越来越多的研究证据表明，TBC结构域家族（TBC domain family）参与了包括卵巢癌在内的多种癌症发生发展相关的各类细胞生物学过程。然而，作为TBC结构域家族关键成员的TBC1D2在卵巢癌中的作用仍未明确。
方法：本研究采用免疫组化（Immunohistochemistry, IHC）和实时荧光定量聚合酶链反应（quantitative real-time polymerase chain reaction, qRT-PCR）检测卵巢癌组织与细胞中TBC1D2的表达水平；通过体外及体内实验，探究TBC1D2在卵巢癌发生发展中的作用，实验涵盖细胞增殖、迁移与侵袭检测；借助生物信息学分析、蛋白质印迹（Western blotting）及免疫共沉淀（co-immunoprecipitation）技术，阐明TBC1D2促进卵巢癌转移的潜在分子机制。
结果：研究发现，卵巢癌组织中TBC1D2表达上调，且与不良预后显著相关。同时，TBC1D2可在体外促进卵巢癌细胞增殖、迁移与侵袭，并在体内加速肿瘤生长与转移。进一步机制研究显示，TBC1D2通过解离Rac1-IQGAP1复合物，介导E-钙粘蛋白（E-cadherin）降解，从而促进卵巢癌细胞侵袭；此外，本研究筛选并鉴定出miR-373-3p可通过负向调控TBC1D2的表达，抑制OVCAR3细胞的侵袭能力。
结论：本研究结果表明，TBC1D2在卵巢癌中呈过表达状态，并通过介导E-钙粘蛋白降解促进肿瘤转移；本研究提示TBC1D2有望成为卵巢癌潜在的治疗靶点。