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SEC23A confers ER stress resistance in gastric cancer by forming the ER stress-SEC23A-autophagy negative feedback loop

BACKGROUND: Sec23 homolog A (SEC23A), a core component of coat protein complex II (COPII), has been reported to be involved in several cancers. However, the role of SEC23A in gastric cancer remains unclear. METHODS: The expression of SEC23A in gastric cancer was analyzed by using qRT-PCR, western bl...

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Autores principales: Cheng, Quan, Liu, Kanghui, Xiao, Jian, Shen, Kuan, Wang, Yuanhang, Zhou, Xinyi, Wang, Jiawei, Xu, Zekuan, Yang, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478313/
https://www.ncbi.nlm.nih.gov/pubmed/37670384
http://dx.doi.org/10.1186/s13046-023-02807-w
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author Cheng, Quan
Liu, Kanghui
Xiao, Jian
Shen, Kuan
Wang, Yuanhang
Zhou, Xinyi
Wang, Jiawei
Xu, Zekuan
Yang, Li
author_facet Cheng, Quan
Liu, Kanghui
Xiao, Jian
Shen, Kuan
Wang, Yuanhang
Zhou, Xinyi
Wang, Jiawei
Xu, Zekuan
Yang, Li
author_sort Cheng, Quan
collection PubMed
description BACKGROUND: Sec23 homolog A (SEC23A), a core component of coat protein complex II (COPII), has been reported to be involved in several cancers. However, the role of SEC23A in gastric cancer remains unclear. METHODS: The expression of SEC23A in gastric cancer was analyzed by using qRT-PCR, western blotting and IHC staining. The role of SEC23A in ER stress resistance was explored by functional experiments in vitro and vivo. The occupation of STAT3 on the SEC23A promoter region was verified by luciferase reporter plasmids and CHIP assay. The interaction between SEC23A and ANXA2 was identified by Co-IP and mass spectrometry analysis. RESULTS: We demonstrated that SEC23A was upregulated in gastric cancer and predicted poor prognosis in patients with gastric cancer. Mechanistically, SEC23A was transcriptional upregulated by ER stress-induced pY705-STAT3. Highly expressed SEC23A promoted autophagy by regulating the cellular localization of ANXA2. The SEC23A-ANXA2-autophay axis, in turn, protected gastric cancer cells from ER stress-induced apoptosis. Furthermore, we identified SEC23A attenuated 5-FU therapeutic effectiveness in gastric cancer cells through autophagy-mediated ER stress relief. CONCLUSION: We reveal an ER stress-SEC23A-autophagy negative feedback loop that enhances the ability of gastric cancer cells to resist the adverse survival environments. These results identify SEC23A as a promising molecular target for potential therapeutic intervention and prognostic prediction in patients with gastric cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-023-02807-w.
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spelling pubmed-104783132023-09-06 SEC23A confers ER stress resistance in gastric cancer by forming the ER stress-SEC23A-autophagy negative feedback loop Cheng, Quan Liu, Kanghui Xiao, Jian Shen, Kuan Wang, Yuanhang Zhou, Xinyi Wang, Jiawei Xu, Zekuan Yang, Li J Exp Clin Cancer Res Research BACKGROUND: Sec23 homolog A (SEC23A), a core component of coat protein complex II (COPII), has been reported to be involved in several cancers. However, the role of SEC23A in gastric cancer remains unclear. METHODS: The expression of SEC23A in gastric cancer was analyzed by using qRT-PCR, western blotting and IHC staining. The role of SEC23A in ER stress resistance was explored by functional experiments in vitro and vivo. The occupation of STAT3 on the SEC23A promoter region was verified by luciferase reporter plasmids and CHIP assay. The interaction between SEC23A and ANXA2 was identified by Co-IP and mass spectrometry analysis. RESULTS: We demonstrated that SEC23A was upregulated in gastric cancer and predicted poor prognosis in patients with gastric cancer. Mechanistically, SEC23A was transcriptional upregulated by ER stress-induced pY705-STAT3. Highly expressed SEC23A promoted autophagy by regulating the cellular localization of ANXA2. The SEC23A-ANXA2-autophay axis, in turn, protected gastric cancer cells from ER stress-induced apoptosis. Furthermore, we identified SEC23A attenuated 5-FU therapeutic effectiveness in gastric cancer cells through autophagy-mediated ER stress relief. CONCLUSION: We reveal an ER stress-SEC23A-autophagy negative feedback loop that enhances the ability of gastric cancer cells to resist the adverse survival environments. These results identify SEC23A as a promising molecular target for potential therapeutic intervention and prognostic prediction in patients with gastric cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-023-02807-w. BioMed Central 2023-09-05 /pmc/articles/PMC10478313/ /pubmed/37670384 http://dx.doi.org/10.1186/s13046-023-02807-w 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Cheng, Quan
Liu, Kanghui
Xiao, Jian
Shen, Kuan
Wang, Yuanhang
Zhou, Xinyi
Wang, Jiawei
Xu, Zekuan
Yang, Li
SEC23A confers ER stress resistance in gastric cancer by forming the ER stress-SEC23A-autophagy negative feedback loop
title SEC23A confers ER stress resistance in gastric cancer by forming the ER stress-SEC23A-autophagy negative feedback loop
title_full SEC23A confers ER stress resistance in gastric cancer by forming the ER stress-SEC23A-autophagy negative feedback loop
title_fullStr SEC23A confers ER stress resistance in gastric cancer by forming the ER stress-SEC23A-autophagy negative feedback loop
title_full_unstemmed SEC23A confers ER stress resistance in gastric cancer by forming the ER stress-SEC23A-autophagy negative feedback loop
title_short SEC23A confers ER stress resistance in gastric cancer by forming the ER stress-SEC23A-autophagy negative feedback loop
title_sort sec23a confers er stress resistance in gastric cancer by forming the er stress-sec23a-autophagy negative feedback loop
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478313/
https://www.ncbi.nlm.nih.gov/pubmed/37670384
http://dx.doi.org/10.1186/s13046-023-02807-w
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