2. Academic Validation
  3. N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells

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

  • Cell Death Dis. 2022 Jul 19;13(7):626. doi: 10.1038/s41419-022-05090-3.
Rong Wang 1 2,  Piaopiao Wen 3,  Ganglong Yang 3,  Yanyan Feng 1 4,  Yuanyuan Mi 4,  Xiaoying Wang 1,  Shenglong Zhu 1,  Yong Q Chen 5 6
Affiliations

Affiliations

  • 1 Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu Province, 214122, China.
  • 2 School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu Province, 214122, China.
  • 3 School of Biological Engineering, Jiangnan University, Wuxi, Jiangsu Province, 214122, China.
  • 4 Department of Urology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, 214122, China.
  • 5 Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu Province, 214122, China. yqchen@jiangnan.edu.cn.
  • 6 School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu Province, 214122, China. yqchen@jiangnan.edu.cn.
PMID: 35853851 DOI: 10.1038/s41419-022-05090-3
Abstract

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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