Details

Autor(en) / Beteiligte

• Bai, Yuchen
• Gotz, Carolin
• Chincarini, Ginevra
• Zhao, Zixuan
• Slaney, Clare
• Boath, Jarryd
• Furic, Luc
• Angel, Christopher
• Jane, Stephen M
• Phillips, Wayne A
• Stacker, Steven A
• Farah, Camile S
• Darido, Charbel

Titel

YBX1 integration of oncogenic PI3K/mTOR signalling regulates the fitness of malignant epithelial cells

Ist Teil von

• Nature communications, 2023-03, Vol.14 (1), p.1591-1591, Article 1591

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.