| Autor: |
Liu, Yen-Nien, Chen, Wei-Yu, Yeh, Hsiu-Lien, Chen, Wei-Hao, Jiang, Kuo-Ching, Li, Han-Ru, Dung, Phan Vu Thuy, Chen, Zi-Qing, Lee, Wei-Jiunn, Hsiao, Michael, Huang, Jiaoti, Wen, Yu-Ching |
| Předmět: |
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| Zdroj: |
Science Signaling; 6/11/2024, Vol. 17 Issue 840, p1-18, 18p |
| Abstrakt: |
Neuroendocrine prostate cancer (PCa) (NEPC), an aggressive subtype that is associated with poor prognosis, may arise after androgen deprivation therapy (ADT). We investigated the molecular mechanisms by which ADT induces neuroendocrine differentiation in advanced PCa. We found that transmembrane protein 1 (MCTP1), which has putative Ca2+ sensing function and multiple Ca2+-binding C2 domains, was abundant in samples from patients with advanced PCa. MCTP1 was associated with the expression of the EMT-associated transcription factors ZBTB46, FOXA2, and HIF1A. The increased abundance of MCTP1 promoted PC3 prostate cancer cell migration and neuroendocrine differentiation and was associated with SNAI1-dependent EMT in C4-2 PCa cells after ADT. ZBTB46 interacted with FOXA2 and HIF1A and increased the abundance of MCTP1 in a hypoxia-dependent manner. MCTP1 stimulated Ca2+ signaling and AKT activation to promote EMT and neuroendocrine differentiation by increasing the SNAI1-dependent expression of EMT and neuroendocrine markers, effects that were blocked by knockdown of MCTP1. These data suggest an oncogenic role for MCTP1 in the maintenance of a rare and aggressive prostate cancer subtype through its response to Ca2+ and suggest its potential as a therapeutic target. Editor's summary: Androgen deprivation therapy is used to treat prostate cancer but can induce its differentiation into an aggressive neuroendocrine subtype with poor clinical outcomes. Liu et al. uncovered a role for the putative Ca2+ sensor MCTP1 in neuroendocrine differentiation in prostate cancer. MCTP1 was abundant in human prostate tumors, and its expression in prostate cancer cells was stimulated by the transcription factors ZBTB46, FOXA2, and HIF1A in a hypoxia-dependent manner. MCTP1 expression promoted tumor progression and epithelial-to-mesenchymal transition, thus suggesting that targeting MCTP1 could prevent neuroendocrine differentiation in prostate cancer. —Amy E. Baek [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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