YBX1 integration of oncogenic PI3K/mTOR signalling regulates the fitness of malignant epithelial cells
Details
Publication Year 2023-03-22,Volume 14,Issue #1,Page 1591
Journal Title
Nature Communications
Publication Type
Research article
Abstract
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.
Publisher
Springer Nature
Keywords
Humans; *Phosphatidylinositol 3-Kinases/genetics/metabolism; *Proto-Oncogene Proteins c-akt/metabolism; Signal Transduction; TOR Serine-Threonine Kinases/genetics/metabolism; Cell Proliferation/genetics; Epithelial Cells/metabolism; Epithelial-Mesenchymal Transition/genetics; Cell Line, Tumor; Cell Movement; Y-Box-Binding Protein 1/genetics/metabolism
Department(s)
Laboratory Research; Pathology
PubMed ID
36949044
Open Access at Publisher's Site
https://doi.org/10.1038/s41467-023-37161-0
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2023-06-22 07:56:49
Last Modified: 2023-06-22 07:57:28

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