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The extracellular SEMA domain attenuates intracellular apoptotic signaling of semaphorin 6A in lung cancer cells

Semaphorin 6A (SEMA6A), a membrane-bound protein, is downregulated in lung cancer tissue compared to its adjacent normal tissue. However, the functions of SEMA6A in lung cancer cells are still unclear. In the present study, full length SEMA6A and various truncations were transfected into lung cancer...

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Autores principales: Shen, Cheng-Ying, Chang, Ya-Chu, Chen, Li-Han, Lin, Wen-Chun, Lee, Yung-Hua, Yeh, Shu-Tsen, Chen, Hsin-Kuang, Fang, Wentao, Hsu, Chung-Ping, Lee, Jang-Ming, Lu, Tzu-Pin, Hsiao, Pei-Wen, Lai, Liang-Chuan, Tsai, Mong-Hsun, Chuang, Eric Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281666/
https://www.ncbi.nlm.nih.gov/pubmed/30518871
http://dx.doi.org/10.1038/s41389-018-0105-z
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author Shen, Cheng-Ying
Chang, Ya-Chu
Chen, Li-Han
Lin, Wen-Chun
Lee, Yung-Hua
Yeh, Shu-Tsen
Chen, Hsin-Kuang
Fang, Wentao
Hsu, Chung-Ping
Lee, Jang-Ming
Lu, Tzu-Pin
Hsiao, Pei-Wen
Lai, Liang-Chuan
Tsai, Mong-Hsun
Chuang, Eric Y.
author_facet Shen, Cheng-Ying
Chang, Ya-Chu
Chen, Li-Han
Lin, Wen-Chun
Lee, Yung-Hua
Yeh, Shu-Tsen
Chen, Hsin-Kuang
Fang, Wentao
Hsu, Chung-Ping
Lee, Jang-Ming
Lu, Tzu-Pin
Hsiao, Pei-Wen
Lai, Liang-Chuan
Tsai, Mong-Hsun
Chuang, Eric Y.
author_sort Shen, Cheng-Ying
collection PubMed
description Semaphorin 6A (SEMA6A), a membrane-bound protein, is downregulated in lung cancer tissue compared to its adjacent normal tissue. However, the functions of SEMA6A in lung cancer cells are still unclear. In the present study, full length SEMA6A and various truncations were transfected into lung cancer cells to investigate the role of the different domains of SEMA6A in cell proliferation and survival, apoptosis, and in vivo tumor growth. SEMA6A-induced cell signaling was explored using gene silencing, co-immunoprecipitation, and co-culture assays. Our results showed that overexpression of SEMA6A reduced the growth of lung cancer cells in vitro and in vivo, and silencing SEMA6A increased the proliferation of normal lung fibroblasts. Truncated SEMA6A lacking the SEMA domain or the extracellular region induced more apoptosis than full length SEMA6A, and reintroducing the SEMA domain attenuated the apoptosis. Fas-associated protein with death domain (FADD) bound to the cytosolic region of truncated SEMA6A and was involved in SEMA6A-associated cytosol-induced apoptosis. This study suggests a novel function of SEMA6A in inducing apoptosis via FADD binding in lung cancer cells.
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spelling pubmed-62816662018-12-06 The extracellular SEMA domain attenuates intracellular apoptotic signaling of semaphorin 6A in lung cancer cells Shen, Cheng-Ying Chang, Ya-Chu Chen, Li-Han Lin, Wen-Chun Lee, Yung-Hua Yeh, Shu-Tsen Chen, Hsin-Kuang Fang, Wentao Hsu, Chung-Ping Lee, Jang-Ming Lu, Tzu-Pin Hsiao, Pei-Wen Lai, Liang-Chuan Tsai, Mong-Hsun Chuang, Eric Y. Oncogenesis Article Semaphorin 6A (SEMA6A), a membrane-bound protein, is downregulated in lung cancer tissue compared to its adjacent normal tissue. However, the functions of SEMA6A in lung cancer cells are still unclear. In the present study, full length SEMA6A and various truncations were transfected into lung cancer cells to investigate the role of the different domains of SEMA6A in cell proliferation and survival, apoptosis, and in vivo tumor growth. SEMA6A-induced cell signaling was explored using gene silencing, co-immunoprecipitation, and co-culture assays. Our results showed that overexpression of SEMA6A reduced the growth of lung cancer cells in vitro and in vivo, and silencing SEMA6A increased the proliferation of normal lung fibroblasts. Truncated SEMA6A lacking the SEMA domain or the extracellular region induced more apoptosis than full length SEMA6A, and reintroducing the SEMA domain attenuated the apoptosis. Fas-associated protein with death domain (FADD) bound to the cytosolic region of truncated SEMA6A and was involved in SEMA6A-associated cytosol-induced apoptosis. This study suggests a novel function of SEMA6A in inducing apoptosis via FADD binding in lung cancer cells. Nature Publishing Group UK 2018-12-05 /pmc/articles/PMC6281666/ /pubmed/30518871 http://dx.doi.org/10.1038/s41389-018-0105-z Text en © The Author(s) 2018 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/.
spellingShingle Article
Shen, Cheng-Ying
Chang, Ya-Chu
Chen, Li-Han
Lin, Wen-Chun
Lee, Yung-Hua
Yeh, Shu-Tsen
Chen, Hsin-Kuang
Fang, Wentao
Hsu, Chung-Ping
Lee, Jang-Ming
Lu, Tzu-Pin
Hsiao, Pei-Wen
Lai, Liang-Chuan
Tsai, Mong-Hsun
Chuang, Eric Y.
The extracellular SEMA domain attenuates intracellular apoptotic signaling of semaphorin 6A in lung cancer cells
title The extracellular SEMA domain attenuates intracellular apoptotic signaling of semaphorin 6A in lung cancer cells
title_full The extracellular SEMA domain attenuates intracellular apoptotic signaling of semaphorin 6A in lung cancer cells
title_fullStr The extracellular SEMA domain attenuates intracellular apoptotic signaling of semaphorin 6A in lung cancer cells
title_full_unstemmed The extracellular SEMA domain attenuates intracellular apoptotic signaling of semaphorin 6A in lung cancer cells
title_short The extracellular SEMA domain attenuates intracellular apoptotic signaling of semaphorin 6A in lung cancer cells
title_sort extracellular sema domain attenuates intracellular apoptotic signaling of semaphorin 6a in lung cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281666/
https://www.ncbi.nlm.nih.gov/pubmed/30518871
http://dx.doi.org/10.1038/s41389-018-0105-z
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