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The activated CD36-Src axis promotes lung adenocarcinoma cell proliferation and actin remodeling-involved metastasis in high-fat environment

Obesity/overweight and lipid metabolism disorders have become increased risk factors for lung cancer. Fatty acid translocase CD36 promotes cellular uptake of fatty acids. Whether and how CD36 facilitates lung adenocarcinoma (LUAD) growth in high-fat environment is unknown. Here, we demonstrated that...

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Autores principales: Liu, Li-Zhong, Wang, Bowen, Zhang, Rui, Wu, Zangshu, Huang, Yuxi, Zhang, Xiaoyang, Zhou, Jiaying, Yi, Junbo, Shen, Jian, Li, Ming-Yue, Dong, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10447533/
https://www.ncbi.nlm.nih.gov/pubmed/37612265
http://dx.doi.org/10.1038/s41419-023-06078-3
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author Liu, Li-Zhong
Wang, Bowen
Zhang, Rui
Wu, Zangshu
Huang, Yuxi
Zhang, Xiaoyang
Zhou, Jiaying
Yi, Junbo
Shen, Jian
Li, Ming-Yue
Dong, Ming
author_facet Liu, Li-Zhong
Wang, Bowen
Zhang, Rui
Wu, Zangshu
Huang, Yuxi
Zhang, Xiaoyang
Zhou, Jiaying
Yi, Junbo
Shen, Jian
Li, Ming-Yue
Dong, Ming
author_sort Liu, Li-Zhong
collection PubMed
description Obesity/overweight and lipid metabolism disorders have become increased risk factors for lung cancer. Fatty acid translocase CD36 promotes cellular uptake of fatty acids. Whether and how CD36 facilitates lung adenocarcinoma (LUAD) growth in high-fat environment is unknown. Here, we demonstrated that palmitic acid (PA) or high-fat diet (HFD) promoted LUAD cell proliferation and metastasis in a CD36-dependent manner. Mechanistically, CD36 translocated from cytoplasm to cell membrane and interacted with Src kinase upon PA stimulation in human LUAD cells. Akt and ERK, downstream of Src, were then activated to mediate LUAD cell proliferation and metastasis. Furthermore, PA treatment promoted CD36 sarcolemmal translocation, where it activated Rac1 and upregulated MMP-9 through Src-Akt/ERK pathway, resulting in redistribution of cortactin, N-WASP and Arp2/3, and finally led to occurrence of finger-like protrusions of actin on cell surface to enhance cell metastasis. Compared with normal-chew diet (NCD) mice, the HFD group exhibited higher level of blood free fatty acid (FFA) and cholesterol (TC), developed larger xenograft LUAD tumors and enhanced tumor cell metastatic potential, which were accompanied by obvious sarcolemmal actin remodeling and were blocked by simultaneous CD36 knockdown in LUAD cells. Consistently, xenografted and tail vein-injected scramble-RNA-A549 cells but not CD36-shRNA-A549 in HFD mice formed metastatic LUAD tumors on the lung. CD36 inhibitor SSO significantly inhibited LUAD cell metastasis to the lung. Collectively, CD36 initiates Src signaling to promote LUAD cell proliferation and actin remodeling-involved metastasis under high-fat environment. Our study provides the new insights that CD36 is a valid target for LUAD therapy. [Image: see text]
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spelling pubmed-104475332023-08-25 The activated CD36-Src axis promotes lung adenocarcinoma cell proliferation and actin remodeling-involved metastasis in high-fat environment Liu, Li-Zhong Wang, Bowen Zhang, Rui Wu, Zangshu Huang, Yuxi Zhang, Xiaoyang Zhou, Jiaying Yi, Junbo Shen, Jian Li, Ming-Yue Dong, Ming Cell Death Dis Article Obesity/overweight and lipid metabolism disorders have become increased risk factors for lung cancer. Fatty acid translocase CD36 promotes cellular uptake of fatty acids. Whether and how CD36 facilitates lung adenocarcinoma (LUAD) growth in high-fat environment is unknown. Here, we demonstrated that palmitic acid (PA) or high-fat diet (HFD) promoted LUAD cell proliferation and metastasis in a CD36-dependent manner. Mechanistically, CD36 translocated from cytoplasm to cell membrane and interacted with Src kinase upon PA stimulation in human LUAD cells. Akt and ERK, downstream of Src, were then activated to mediate LUAD cell proliferation and metastasis. Furthermore, PA treatment promoted CD36 sarcolemmal translocation, where it activated Rac1 and upregulated MMP-9 through Src-Akt/ERK pathway, resulting in redistribution of cortactin, N-WASP and Arp2/3, and finally led to occurrence of finger-like protrusions of actin on cell surface to enhance cell metastasis. Compared with normal-chew diet (NCD) mice, the HFD group exhibited higher level of blood free fatty acid (FFA) and cholesterol (TC), developed larger xenograft LUAD tumors and enhanced tumor cell metastatic potential, which were accompanied by obvious sarcolemmal actin remodeling and were blocked by simultaneous CD36 knockdown in LUAD cells. Consistently, xenografted and tail vein-injected scramble-RNA-A549 cells but not CD36-shRNA-A549 in HFD mice formed metastatic LUAD tumors on the lung. CD36 inhibitor SSO significantly inhibited LUAD cell metastasis to the lung. Collectively, CD36 initiates Src signaling to promote LUAD cell proliferation and actin remodeling-involved metastasis under high-fat environment. Our study provides the new insights that CD36 is a valid target for LUAD therapy. [Image: see text] Nature Publishing Group UK 2023-08-23 /pmc/articles/PMC10447533/ /pubmed/37612265 http://dx.doi.org/10.1038/s41419-023-06078-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Liu, Li-Zhong
Wang, Bowen
Zhang, Rui
Wu, Zangshu
Huang, Yuxi
Zhang, Xiaoyang
Zhou, Jiaying
Yi, Junbo
Shen, Jian
Li, Ming-Yue
Dong, Ming
The activated CD36-Src axis promotes lung adenocarcinoma cell proliferation and actin remodeling-involved metastasis in high-fat environment
title The activated CD36-Src axis promotes lung adenocarcinoma cell proliferation and actin remodeling-involved metastasis in high-fat environment
title_full The activated CD36-Src axis promotes lung adenocarcinoma cell proliferation and actin remodeling-involved metastasis in high-fat environment
title_fullStr The activated CD36-Src axis promotes lung adenocarcinoma cell proliferation and actin remodeling-involved metastasis in high-fat environment
title_full_unstemmed The activated CD36-Src axis promotes lung adenocarcinoma cell proliferation and actin remodeling-involved metastasis in high-fat environment
title_short The activated CD36-Src axis promotes lung adenocarcinoma cell proliferation and actin remodeling-involved metastasis in high-fat environment
title_sort activated cd36-src axis promotes lung adenocarcinoma cell proliferation and actin remodeling-involved metastasis in high-fat environment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10447533/
https://www.ncbi.nlm.nih.gov/pubmed/37612265
http://dx.doi.org/10.1038/s41419-023-06078-3
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