YBX1 integration of oncogenic PI3K/mTOR signalling regulates the fitness of malignant epithelial cells.
Humans
Phosphatidylinositol 3-Kinases
/ genetics
Proto-Oncogene Proteins c-akt
/ metabolism
Signal Transduction
TOR Serine-Threonine Kinases
/ genetics
Cell Proliferation
/ genetics
Epithelial Cells
/ metabolism
Epithelial-Mesenchymal Transition
/ genetics
Cell Line, Tumor
Cell Movement
Y-Box-Binding Protein 1
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 03 2023
22 03 2023
Historique:
received:
25
05
2022
accepted:
06
03
2023
entrez:
23
3
2023
pubmed:
24
3
2023
medline:
25
3
2023
Statut:
epublish
Résumé
In heterogeneous head and neck cancer (HNC), subtype-specific treatment regimens are currently missing. An integrated analysis of patient HNC subtypes using single-cell sequencing and proteome profiles reveals an epithelial-mesenchymal transition (EMT) signature within the epithelial cancer-cell population. The EMT signature coincides with PI3K/mTOR inactivation in the mesenchymal subtype. Conversely, the signature is suppressed in epithelial cells of the basal subtype which exhibits hyperactive PI3K/mTOR signalling. We further identify YBX1 phosphorylation, downstream of the PI3K/mTOR pathway, restraining basal-like cancer cell proliferation. In contrast, YBX1 acts as a safeguard against the proliferation-to-invasion switch in mesenchymal-like epithelial cancer cells, and its loss accentuates partial-EMT and in vivo invasion. Interestingly, phospho-YBX1 that is mutually exclusive to partial-EMT, emerges as a prognostic marker for overall patient outcomes. These findings create a unique opportunity to sensitise mesenchymal cancer cells to PI3K/mTOR inhibitors by shifting them towards a basal-like subtype as a promising therapeutic approach against HNC.
Identifiants
pubmed: 36949044
doi: 10.1038/s41467-023-37161-0
pii: 10.1038/s41467-023-37161-0
pmc: PMC10033729
doi:
Substances chimiques
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
MTOR protein, human
EC 2.7.1.1
YBX1 protein, human
0
Y-Box-Binding Protein 1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1591Informations de copyright
© 2023. The Author(s).
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