Castration-Induced Downregulation of SPARC in Stromal Cells Drives Neuroendocrine Differentiation of Prostate Cancer.
Animals
Biomarkers, Tumor
/ metabolism
Cell Differentiation
Cell Line, Tumor
Coculture Techniques
Down-Regulation
Endoplasmic Reticulum Chaperone BiP
/ metabolism
Epigenesis, Genetic
Gene Expression Regulation, Neoplastic
Humans
Male
Mice
Mice, Inbred C57BL
Neuroendocrine Cells
/ metabolism
Osteonectin
/ biosynthesis
Prostatic Neoplasms
/ metabolism
Stromal Cells
/ metabolism
Transgenes
Tumor Microenvironment
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
15 08 2021
15 08 2021
Historique:
received:
15
01
2021
revised:
28
01
2021
accepted:
18
06
2021
pubmed:
30
6
2021
medline:
8
1
2022
entrez:
29
6
2021
Statut:
ppublish
Résumé
Fatal neuroendocrine differentiation (NED) of castration-resistant prostate cancer is a recurrent mechanism of resistance to androgen deprivation therapies (ADT) and antiandrogen receptor pathway inhibitors (ARPI) in patients. The design of effective therapies for neuroendocrine prostate cancer (NEPC) is complicated by limited knowledge of the molecular mechanisms governing NED. The paucity of acquired genomic alterations and the deregulation of epigenetic and transcription factors suggest a potential contribution from the microenvironment. In this context, whether ADT/ARPI induces stromal cells to release NED-promoting molecules and the underlying molecular networks are unestablished. Here, we utilized transgenic and transplantable mouse models and coculture experiments to unveil a novel tumor-stroma cross-talk that is able to induce NED under the pressure of androgen deprivation. Castration induced upregulation of GRP78 in tumor cells, which triggers
Identifiants
pubmed: 34185677
pii: 0008-5472.CAN-21-0163
doi: 10.1158/0008-5472.CAN-21-0163
pmc: PMC9398117
doi:
Substances chimiques
Biomarkers, Tumor
0
Endoplasmic Reticulum Chaperone BiP
0
HSPA5 protein, human
0
Hspa5 protein, mouse
0
Osteonectin
0
SPARC protein, human
0
SPARC protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4257-4274Informations de copyright
©2021 The Authors; Published by the American Association for Cancer Research.
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