TRAF6 regulates autophagy and apoptosis of melanoma cells through c‐Jun/ATG16L2 signaling pathway
Abstract 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 offer...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-08-01
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| Series: | MedComm |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mco2.309 |
| _version_ | 1797693067005788160 |
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| author | Yeye Guo Xu Zhang Jie Li Zhe Zhou Susi Zhu Waner Liu Juan Su Xiang Chen Cong Peng |
| author_facet | Yeye Guo Xu Zhang Jie Li Zhe Zhou Susi Zhu Waner Liu Juan Su Xiang Chen Cong Peng |
| author_sort | Yeye Guo |
| collection | DOAJ |
| description | Abstract 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 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. |
| first_indexed | 2024-03-12T02:38:14Z |
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| id | doaj.art-54593b37b3814a95aabb231a4e42fc50 |
| institution | Directory Open Access Journal |
| issn | 2688-2663 |
| language | English |
| last_indexed | 2024-03-12T02:38:14Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj.art-54593b37b3814a95aabb231a4e42fc502023-09-04T11:20:36ZengWileyMedComm2688-26632023-08-0144n/an/a10.1002/mco2.309TRAF6 regulates autophagy and apoptosis of melanoma cells through c‐Jun/ATG16L2 signaling pathwayYeye Guo0Xu Zhang1Jie Li2Zhe Zhou3Susi Zhu4Waner Liu5Juan Su6Xiang Chen7Cong Peng8Department of Dermatology Xiangya Hospital Central South University Changsha ChinaDepartment of Dermatology Xiangya Hospital Central South University Changsha ChinaDepartment of Dermatology Xiangya Hospital Central South University Changsha ChinaDepartment of Dermatology Xiangya Hospital Central South University Changsha ChinaDepartment of Dermatology Xiangya Hospital Central South University Changsha ChinaDepartment of Dermatology Xiangya Hospital Central South University Changsha ChinaDepartment of Dermatology Xiangya Hospital Central South University Changsha ChinaDepartment of Dermatology Xiangya Hospital Central South University Changsha ChinaDepartment of Dermatology Xiangya Hospital Central South University Changsha ChinaAbstract 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 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.https://doi.org/10.1002/mco2.309apoptosisATG16L2autophagyc‐JunmelanomaTRAF6 |
| spellingShingle | Yeye Guo Xu Zhang Jie Li Zhe Zhou Susi Zhu Waner Liu Juan Su Xiang Chen Cong Peng TRAF6 regulates autophagy and apoptosis of melanoma cells through c‐Jun/ATG16L2 signaling pathway MedComm apoptosis ATG16L2 autophagy c‐Jun melanoma TRAF6 |
| title | TRAF6 regulates autophagy and apoptosis of melanoma cells through c‐Jun/ATG16L2 signaling pathway |
| title_full | TRAF6 regulates autophagy and apoptosis of melanoma cells through c‐Jun/ATG16L2 signaling pathway |
| title_fullStr | TRAF6 regulates autophagy and apoptosis of melanoma cells through c‐Jun/ATG16L2 signaling pathway |
| title_full_unstemmed | TRAF6 regulates autophagy and apoptosis of melanoma cells through c‐Jun/ATG16L2 signaling pathway |
| title_short | TRAF6 regulates autophagy and apoptosis of melanoma cells through c‐Jun/ATG16L2 signaling pathway |
| title_sort | traf6 regulates autophagy and apoptosis of melanoma cells through c jun atg16l2 signaling pathway |
| topic | apoptosis ATG16L2 autophagy c‐Jun melanoma TRAF6 |
| url | https://doi.org/10.1002/mco2.309 |
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