Guo Yeye, Zhang Xu, Li Jie, Zhou Zhe, Zhu Susi, Liu Waner, Su Juan, Chen Xiang, Peng Cong
Department of Dermatology Xiangya Hospital Central South University Changsha China.
National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology Changsha China.
MedComm (2020). 2023 Jul 20;4(4):e309. doi: 10.1002/mco2.309. eCollection 2023 Aug.
Autophagy and apoptosis are essential processes that participate in cell death and maintain cellular homeostasis. Dysregulation of these biological processes results in the development of diseases, including cancers. Therefore, targeting the interaction between apoptosis and autophagy offers a potential strategy for cancer therapy. Melanoma is the most lethal skin cancer. We previously found that tumor necrosis factor receptor-associated factor 6 (TRAF6) is overexpressed in melanoma and benefits the malignant phenotype of melanoma cells. Additionally, TRAF6 promotes the activation of cancer-associated fibroblasts in melanoma. However, the role of TRAF6 in autophagy and apoptosis remains unclear. In this study, we found that knockdown of TRAF6 induced both apoptosis and autophagy in melanoma cells. Transcriptomic data and real-time PCR analysis demonstrated reduced expression of 2 () in TRAF6-deficient melanoma cells. knockdown resulted in increased autophagy and apoptosis. Mechanism studies confirmed that TRAF6 regulated expression through c-Jun. Importantly, targeting TRAF6 with cinchonine, a TRAF6 inhibitor, effectively suppressed the growth of melanoma cells by inducing autophagy and apoptosis through the TRAF6/c-Jun/ATG16L2 signaling pathway. These findings highlight the pivotal role of TRAF6 in regulating autophagy and apoptosis in melanoma, emphasizing its significance as a novel therapeutic target for melanoma treatment.
自噬和凋亡是参与细胞死亡并维持细胞内稳态的重要过程。这些生物学过程的失调会导致包括癌症在内的疾病的发生。因此，针对凋亡与自噬之间的相互作用提供了一种潜在的癌症治疗策略。黑色素瘤是最致命的皮肤癌。我们之前发现肿瘤坏死因子受体相关因子6（TRAF6）在黑色素瘤中过表达，并有利于黑色素瘤细胞的恶性表型。此外，TRAF6促进黑色素瘤中癌症相关成纤维细胞的活化。然而，TRAF6在自噬和凋亡中的作用仍不清楚。在本研究中，我们发现敲低TRAF6可诱导黑色素瘤细胞发生凋亡和自噬。转录组数据和实时PCR分析表明，在缺乏TRAF6的黑色素瘤细胞中2（）的表达降低。敲低导致自噬和凋亡增加。机制研究证实，TRAF6通过c-Jun调节表达。重要的是，用TRAF6抑制剂辛可宁靶向TRAF6，通过TRAF6/c-Jun/ATG16L2信号通路诱导自噬和凋亡，有效抑制了黑色素瘤细胞的生长。这些发现突出了TRAF6在调节黑色素瘤自噬和凋亡中的关键作用，强调了其作为黑色素瘤治疗新靶点的重要性。
