MCTP1 increases the malignancy of androgen-deprived prostate cancer cells by inducing neuroendocrine differentiation and EMT.
Sci Signal
; 17(840): eadc9142, 2024 Jun 11.
Article
in En
| MEDLINE
| ID: mdl-38861615
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prostatic Neoplasms
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Cell Differentiation
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Epithelial-Mesenchymal Transition
Limits:
Animals
/
Humans
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Male
Language:
En
Journal:
Sci Signal
Journal subject:
CIENCIA
/
FISIOLOGIA
Year:
2024
Document type:
Article
Affiliation country: