N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells

Castration-resistance of prostate cancer is one of the most challenging clinical problems. In the present study, we have performed proteomics and glycomics using LNCaP model. Growth differentiation factor-15 (GDF15) level is increased in androgen receptor (AR) inhibitor-resistant cells and the inhib...

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Autores principales: Wang, Rong, Wen, Piaopiao, Yang, Ganglong, Feng, Yanyan, Mi, Yuanyuan, Wang, Xiaoying, Zhu, Shenglong, Chen, Yong Q.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296468/
https://www.ncbi.nlm.nih.gov/pubmed/35853851
http://dx.doi.org/10.1038/s41419-022-05090-3
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author Wang, Rong
Wen, Piaopiao
Yang, Ganglong
Feng, Yanyan
Mi, Yuanyuan
Wang, Xiaoying
Zhu, Shenglong
Chen, Yong Q.
author_facet Wang, Rong
Wen, Piaopiao
Yang, Ganglong
Feng, Yanyan
Mi, Yuanyuan
Wang, Xiaoying
Zhu, Shenglong
Chen, Yong Q.
author_sort Wang, Rong
collection PubMed
description Castration-resistance of prostate cancer is one of the most challenging clinical problems. In the present study, we have performed proteomics and glycomics using LNCaP model. Growth differentiation factor-15 (GDF15) level is increased in androgen receptor (AR) inhibitor-resistant cells and the inhibitory effect of GDF15 on epithelial growth factor receptor (EGFR) pathway is relieved by GDF15 N70 glycosylation. Interference of GDF15 (siRNA or N70Q dominant negative) or EGFR pathway (inhibitor or siRNA for EGFR, SRC or ERK) decreases the resistant-cell survival in culture and tumor growth in mice. Our study reveals a novel regulatory mechanism of prostate cancer AR inhibitor resistance, raises the possibility of AR/SRC dual-targeting of castration-resistance of prostate cancer, and lays foundation for the future development of selective inhibitors of GDF15 glycosylation.
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spelling pubmed-92964682022-07-21 N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells Wang, Rong Wen, Piaopiao Yang, Ganglong Feng, Yanyan Mi, Yuanyuan Wang, Xiaoying Zhu, Shenglong Chen, Yong Q. Cell Death Dis Article Castration-resistance of prostate cancer is one of the most challenging clinical problems. In the present study, we have performed proteomics and glycomics using LNCaP model. Growth differentiation factor-15 (GDF15) level is increased in androgen receptor (AR) inhibitor-resistant cells and the inhibitory effect of GDF15 on epithelial growth factor receptor (EGFR) pathway is relieved by GDF15 N70 glycosylation. Interference of GDF15 (siRNA or N70Q dominant negative) or EGFR pathway (inhibitor or siRNA for EGFR, SRC or ERK) decreases the resistant-cell survival in culture and tumor growth in mice. Our study reveals a novel regulatory mechanism of prostate cancer AR inhibitor resistance, raises the possibility of AR/SRC dual-targeting of castration-resistance of prostate cancer, and lays foundation for the future development of selective inhibitors of GDF15 glycosylation. Nature Publishing Group UK 2022-07-19 /pmc/articles/PMC9296468/ /pubmed/35853851 http://dx.doi.org/10.1038/s41419-022-05090-3 Text en © The Author(s) 2022 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
Wang, Rong
Wen, Piaopiao
Yang, Ganglong
Feng, Yanyan
Mi, Yuanyuan
Wang, Xiaoying
Zhu, Shenglong
Chen, Yong Q.
N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells
title N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells
title_full N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells
title_fullStr N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells
title_full_unstemmed N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells
title_short N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells
title_sort n-glycosylation of gdf15 abolishes its inhibitory effect on egfr in ar inhibitor-resistant prostate cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296468/
https://www.ncbi.nlm.nih.gov/pubmed/35853851
http://dx.doi.org/10.1038/s41419-022-05090-3
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