The role of the p90 ribosomal S6 kinase family in prostate cancer progression and therapy resistance.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
27
11
2020
accepted:
20
04
2021
revised:
08
04
2021
pubmed:
12
5
2021
medline:
13
1
2022
entrez:
11
5
2021
Statut:
ppublish
Résumé
Prostate cancer (PCa) is the second most commonly occurring cancer in men, with over a million new cases every year worldwide. Tumor growth and disease progression is mainly dependent on the Androgen Receptor (AR), a ligand dependent transcription factor. Standard PCa therapeutic treatments include androgen-deprivation therapy and AR signaling inhibitors. Despite being successful in controlling the disease in the majority of men, the high frequency of disease progression to aggressive and therapy resistant stages (termed castrate resistant prostate cancer) has led to the search for new therapeutic targets. The p90 ribosomal S6 kinase (RSK1-4) family is a group of highly conserved Ser/Thr kinases that holds promise as a novel target. RSKs are effector kinases that lay downstream of the Ras/Raf/MEK/ERK signaling pathway, and aberrant activation or expression of RSKs has been reported in several malignancies, including PCa. Despite their structural similarities, RSK isoforms have been shown to perform nonredundant functions and target a wide range of substrates involved in regulation of transcription and translation. In this article we review the roles of the RSKs in proliferation and motility, cell cycle control and therapy resistance in PCa, highlighting the possible interplay between RSKs and AR in mediating disease progression. In addition, we summarize the current advances in RSK inhibitor development and discuss their potential clinical benefits.
Identifiants
pubmed: 33972681
doi: 10.1038/s41388-021-01810-9
pii: 10.1038/s41388-021-01810-9
pmc: PMC8175238
mid: EMS123046
doi:
Substances chimiques
AR protein, human
0
Androgen Antagonists
0
Receptors, Androgen
0
Ribosomal Protein S6 Kinases, 90-kDa
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
3775-3785Subventions
Organisme : Wellcome Trust
ID : 205767
Pays : United Kingdom
Organisme : Wellcome Trust (Wellcome)
ID : 205767/Z/16/Z
Organisme : Wellcome Trust
Pays : United Kingdom
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