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

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 poten...

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Autores principales: Guo, Yeye, Zhang, Xu, Li, Jie, Zhou, Zhe, Zhu, Susi, Liu, Waner, Su, Juan, Chen, Xiang, Peng, Cong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10357248/
https://www.ncbi.nlm.nih.gov/pubmed/37484971
http://dx.doi.org/10.1002/mco2.309
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author Guo, Yeye
Zhang, Xu
Li, Jie
Zhou, Zhe
Zhu, Susi
Liu, Waner
Su, Juan
Chen, Xiang
Peng, Cong
author_facet Guo, Yeye
Zhang, Xu
Li, Jie
Zhou, Zhe
Zhu, Susi
Liu, Waner
Su, Juan
Chen, Xiang
Peng, Cong
author_sort Guo, Yeye
collection PubMed
description 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.
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spelling pubmed-103572482023-07-21 TRAF6 regulates autophagy and apoptosis of melanoma cells through c‐Jun/ATG16L2 signaling pathway Guo, Yeye Zhang, Xu Li, Jie Zhou, Zhe Zhu, Susi Liu, Waner Su, Juan Chen, Xiang Peng, Cong MedComm (2020) Original Articles 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. John Wiley and Sons Inc. 2023-07-20 /pmc/articles/PMC10357248/ /pubmed/37484971 http://dx.doi.org/10.1002/mco2.309 Text en © 2023 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Guo, Yeye
Zhang, Xu
Li, Jie
Zhou, Zhe
Zhu, Susi
Liu, Waner
Su, Juan
Chen, Xiang
Peng, Cong
TRAF6 regulates autophagy and apoptosis of melanoma cells through c‐Jun/ATG16L2 signaling pathway
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 Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10357248/
https://www.ncbi.nlm.nih.gov/pubmed/37484971
http://dx.doi.org/10.1002/mco2.309
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