Haicang Hospital, No. 89 Haiyu Road, Haicang District, Xiamen, China.
Biomed Res Int. 2021 Aug 6;2021:3431245. doi: 10.1155/2021/3431245. eCollection 2021.
TRAF6 has been reported to be associated with poor prognosis in non-small-cell lung cancer (NSCLC). However, its precise role in tumor development has not been elaborated. In the present study, the function and the mechanism by which TRAF6 contributes to development were intensively investigated. TRAF6 was found to be overexpressed in primary NSCLC tumor tissue and all tested cell lines. Knockdown of TRAF6 with shRNA substantially attenuated NSCLC cell proliferation and anchorage-independent growth. Moreover, tumor glycolysis, such as glucose consumption and lactate production, also significantly impaired. In TRAF6-deficient cells, hexokinase-2 expression was significantly reduced, which was caused by the decrease of HIF-1 transcriptional activity. Further investigations demonstrated that TRAF6 played an important role in the regulation of Akt activation, and exogenous overexpression of constitutively activated Akt substantially rescued glycolysis suppression in TRAF6 knockdown cells. The results of the xenograft model confirmed that downregulation of TRAF6 in NSCLC tumor cells dramatically restrained tumor growth in vivo. Taken together, our studies revealed the mechanism by which TRAF6 exerts its role in NSCLC development and suggested TRAF6 maybe was a promising candidate target for lung cancer prevention and therapy.
TRAF6 已被报道与非小细胞肺癌（NSCLC）的预后不良有关。然而，其在肿瘤发展中的确切作用尚未详细阐明。在本研究中，深入研究了 TRAF6 促进肿瘤发展的功能和机制。研究发现，TRAF6 在原发性 NSCLC 肿瘤组织和所有测试的细胞系中均过表达。用 shRNA 敲低 TRAF6 可显著抑制 NSCLC 细胞的增殖和锚定非依赖性生长。此外，肿瘤糖酵解，如葡萄糖消耗和乳酸生成，也显著受损。在 TRAF6 缺陷细胞中，己糖激酶-2 的表达显著降低，这是由于 HIF-1 转录活性的降低所致。进一步的研究表明，TRAF6 在 Akt 激活的调节中发挥重要作用，外源性过表达组成性激活的 Akt 可显著挽救 TRAF6 敲低细胞中糖酵解的抑制。异种移植模型的结果证实，下调 NSCLC 肿瘤细胞中的 TRAF6 可显著抑制体内肿瘤生长。总之，我们的研究揭示了 TRAF6 在 NSCLC 发展中发挥作用的机制，并表明 TRAF6 可能是预防和治疗肺癌的有前途的候选靶点。
