Abstract
AbstractCastration-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.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology
Reference45 articles.
1. Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res. 1941;1:293–7.
2. Banefelt J, Liede A, Mesterton J, Stalhammar J, Hernandez RK, Sobocki P, et al. Survival and clinical metastases among prostate cancer patients treated with androgen deprivation therapy in Sweden. Cancer Epidemiol. 2014;38:442–7.
3. Rebello RJ, Oing C, Knudsen KE, Loeb S, Johnson DC, Reiter RE, et al. Prostate cancer. Nat Rev Dis Prim. 2021;7:9.
4. Schmidt KT, Huitema ADR, Chau CH, Figg WD. Resistance to second-generation androgen receptor antagonists in prostate cancer. Nat Rev Urol. 2021;18:209–26.
5. Wang Y, Gao W, Li Y, Chow ST, Xie W, Zhang X, et al. Interplay between orphan nuclear receptors and androgen receptor-dependent or-independent growth signalings in prostate cancer. Mol Asp Med. 2021;78:100921.
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