Tumor necrosis factor receptor-associated factor 6 contributes to malignant behavior of human cancers through promoting AKT ubiquitination and phosphorylation
Tumor necrosis factor receptor-associated factor 6 contributes to malignant behavior of human cancers through promoting AKT ubiquitination and phosphorylation
复制标题
肿瘤坏死因子受体相关因子 6 通过促进 AKT 泛素化和磷酸化促进人类癌症的恶性行为
作者：
Shi Jianbo;Liu Zengying;Xu Qin
肿瘤坏死因子受体相关因子6（TRAF 6）已被发现参与多种癌症的致癌作用。然而，TRAF 6在癌症中的确切作用尚未得到广泛研究，并且在很大程度上仍然未知。在这项研究中，我们的目的是研究TRAF 6的生物学功能及其在癌症中的潜在分子机制。在口腔癌和乳腺癌中均观察到肿瘤分化不良与TRAF 6表达状态之间呈正相关。TRAF 6的过表达促进肿瘤细胞的增殖、迁移和G 0/G1向S期的转变。肿瘤坏死因子受体相关因子6介导的AKT泛素化和随后的磷酸化在肿瘤细胞恶性行为的控制中起着至关重要的作用。用TRAF 6而不是E3连接酶缺陷型TRAF 6突变体的体内治疗促进肿瘤生长。我们的研究结果表明，TRAF 6通过促进AKT泛素化和磷酸化促进人类癌症的恶性行为。因此，TRAF 6可以作为癌症的治疗靶点。
Tumor necrosis factor receptor‐associated factor 6 (TRAF6) has been found to be involved in carcinogenesis in multiple cancers. However, the precise role of TRAF6 in cancer has not been extensively investigated and remains largely unknown. In this study, we aimed to investigate the biological function of TRAF6 and its underlying molecular mechanisms in cancer. A positive correlation between poor tumor differentiation and TRAF6 expression status was observed in both oral cancer and breast cancer. Overexpression of TRAF6 promoted proliferation, migration, and G0/G1to S phase transition in tumor cells. Tumor necrosis factor receptor‐associated factor 6‐mediated AKT ubiquitination and subsequent phosphorylation played an essential role in the control of tumor cell malignant behavior. In vivo treatment with TRAF6, but not the E3 ligase deficient TRAF6 mutant, facilitated tumor growth. Our findings indicate that TRAF6 contributes to malignant behavior of human cancers through promoting AKT ubiquitination and phosphorylation. Therefore, TRAF6 could serve as a therapeutic target in cancers.