1. Single-cell analysis reveals androgen receptor regulates the ER-to-Golgi trafficking pathway with CREB3L2 to drive prostate cancer progression.
- Author
-
Hu L, Chen X, Narwade N, Lim MGL, Chen Z, Tennakoon C, Guan P, Chan UI, Zhao Z, Deng M, Xu X, Sung WK, and Cheung E
- Subjects
- Animals, Apoptosis, Basic-Leucine Zipper Transcription Factors genetics, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Cell Proliferation, Endoplasmic Reticulum drug effects, Endoplasmic Reticulum metabolism, Gene Regulatory Networks, Golgi Apparatus drug effects, Golgi Apparatus metabolism, Humans, Male, Mice, Prognosis, Prostatic Neoplasms drug therapy, Prostatic Neoplasms genetics, Prostatic Neoplasms metabolism, Receptors, Androgen genetics, Single-Cell Analysis methods, Survival Rate, Transcriptome, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Androgens pharmacology, Basic-Leucine Zipper Transcription Factors metabolism, Endoplasmic Reticulum pathology, Gene Expression Regulation, Neoplastic drug effects, Golgi Apparatus pathology, Prostatic Neoplasms pathology, Receptors, Androgen metabolism
- Abstract
Androgen receptor (AR) plays a central role in driving prostate cancer (PCa) progression. How AR promotes this process is still not completely clear. Herein, we used single-cell transcriptome analysis to reconstruct the transcriptional network of AR in PCa. Our work shows AR directly regulates a set of signature genes in the ER-to-Golgi protein vesicle-mediated transport pathway. The expression of these genes is required for maximum androgen-dependent ER-to-Golgi trafficking, cell growth, and survival. Our analyses also reveal the signature genes are associated with PCa progression and prognosis. Moreover, we find inhibition of the ER-to-Golgi transport process with a small molecule enhanced antiandrogen-mediated tumor suppression of hormone-sensitive and insensitive PCa. Finally, we demonstrate AR collaborates with CREB3L2 in mediating ER-to-Golgi trafficking in PCa. In summary, our findings uncover a critical role for dysregulation of ER-to-Golgi trafficking expression and function in PCa progression, provide detailed mechanistic insights for how AR tightly controls this process, and highlight the prospect of targeting the ER-to-Golgi pathway as a therapeutic strategy for advanced PCa., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2021
- Full Text
- View/download PDF