MBTPS2 acts as a regulator of lipogenesis and cholesterol synthesis through SREBP signalling in prostate cancer.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
19
08
2022
accepted:
14
03
2023
revised:
10
03
2023
medline:
25
5
2023
pubmed:
30
3
2023
entrez:
29
3
2023
Statut:
ppublish
Résumé
Prostate cancer is the most common cancer in men in the developed world, with most deaths caused by advanced and metastatic disease which has no curative options. Here, we identified Mbtps2 alteration to be associated with metastatic disease in an unbiased in vivo screen and demonstrated its regulation of fatty acid and cholesterol metabolism. The Sleeping Beauty transposon system was used to randomly alter gene expression in the Pten Mbtps2 was identified in our transposon-mediated in vivo screen to be associated with metastatic prostate cancer. Silencing of MBTPS2 expression in LNCaP, DU145 and PC3 human prostate cancer cells reduced proliferation and colony forming growth in vitro. Knockdown of MBTPS2 expression in LNCaP cells impaired cholesterol synthesis and uptake along with reduced expression of key regulators of fatty acid synthesis, namely FASN and ACACA. MBTPS2 is implicated in progressive prostate cancer and may mechanistically involve its effects on fatty acid and cholesterol metabolism.
Sections du résumé
BACKGROUND
Prostate cancer is the most common cancer in men in the developed world, with most deaths caused by advanced and metastatic disease which has no curative options. Here, we identified Mbtps2 alteration to be associated with metastatic disease in an unbiased in vivo screen and demonstrated its regulation of fatty acid and cholesterol metabolism.
METHODS
The Sleeping Beauty transposon system was used to randomly alter gene expression in the Pten
RESULTS
Mbtps2 was identified in our transposon-mediated in vivo screen to be associated with metastatic prostate cancer. Silencing of MBTPS2 expression in LNCaP, DU145 and PC3 human prostate cancer cells reduced proliferation and colony forming growth in vitro. Knockdown of MBTPS2 expression in LNCaP cells impaired cholesterol synthesis and uptake along with reduced expression of key regulators of fatty acid synthesis, namely FASN and ACACA.
CONCLUSION
MBTPS2 is implicated in progressive prostate cancer and may mechanistically involve its effects on fatty acid and cholesterol metabolism.
Identifiants
pubmed: 36991255
doi: 10.1038/s41416-023-02237-7
pii: 10.1038/s41416-023-02237-7
pmc: PMC10205813
doi:
Substances chimiques
Sterol Regulatory Element Binding Protein 1
0
Cholesterol
97C5T2UQ7J
Fatty Acids
0
MBTPS2 protein, human
EC 3.4.24.85
Metalloendopeptidases
EC 3.4.24.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1991-1999Informations de copyright
© 2023. The Author(s).
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