TRAF6 regulates autophagy and apoptosis of melanoma cells through c‐Jun/ATG16L2 signaling pathway

Author:

Guo Yeye12345,Zhang Xu12345,Li Jie12345,Zhou Zhe12345,Zhu Susi12345,Liu Waner12345,Su Juan12345,Chen Xiang12345,Peng Cong12345

Affiliation:

1. Department of Dermatology Xiangya Hospital Central South University Changsha China

2. National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology Changsha China

3. Furong Laboratory Changsha China

4. Hunan Key Laboratory of Skin Cancer and Psoriasis Hunan Engineering Research Center of Skin Health and Disease Xiangya Hospital Central South University Changsha China

5. National Clinical Research Center for Geriatric Disorders (Xiangya Hospital) Changsha China

Abstract

AbstractAutophagy 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 autophagy related 16 like 2 (ATG16L2) in TRAF6‐deficient melanoma cells. ATG16L2 knockdown resulted in increased autophagy and apoptosis. Mechanism studies confirmed that TRAF6 regulated ATG16L2 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.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Hunan Province

National Basic Research Program of China

Publisher

Wiley

Subject

Cell Biology,Biochemistry (medical),Genetics (clinical),Computer Science Applications,Drug Discovery,Genetics,Oncology,Immunology and Allergy

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