The paradoxical role of inositol in cancer: a consequence of the metabolic state of a tumor.
AMPK
Cancer
ISYNA1
Inositol
Metabolism
PI3K-Akt
Journal
Cancer metastasis reviews
ISSN: 1573-7233
Titre abrégé: Cancer Metastasis Rev
Pays: Netherlands
ID NLM: 8605731
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
pubmed:
26
4
2022
medline:
12
8
2022
entrez:
25
4
2022
Statut:
ppublish
Résumé
Inositol is an essential nutrient, obtained either by uptake from the environment or by de novo synthesis from glucose. Inositol and its derivatives exhibit tumor-suppressive effects, potentially mediated by inhibition of the ERK-MAPK or PI3K-Akt pathways. Accordingly, many cancers have been documented to silence expression of the ISYNA1 gene, which encodes the rate-limiting enzyme of inositol synthesis. Paradoxically, recent studies have also reported upregulation of ISYNA1 in some cancers. Upregulation may reflect a compensatory response brought about by defective inositol uptake or oncogenic mutations that preclude its tumor-suppressive effects. In these scenarios, de novo synthesis of inositol may be upregulated to promote cell proliferation. The role of inositol in cancer is further complicated by its ability to inhibit the master metabolic regulator AMPK, which upon activation can either decrease cell proliferation and metastasis or promote cell survival. Due to its potential dual role in cancer, inositol homeostasis must be tightly regulated in tumor cells. Thus, whether inositol acts to suppress or promote tumor progression is determined by the metabolic profile and oncogenic background of the cancer.
Identifiants
pubmed: 35462605
doi: 10.1007/s10555-022-10032-8
pii: 10.1007/s10555-022-10032-8
doi:
Substances chimiques
Inositol
4L6452S749
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
249-254Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM125082
Pays : United States
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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