Journal article
YBX1 integration of oncogenic PI3K/mTOR signalling regulates the fitness of malignant epithelial cells
Y Bai, C Gotz, G Chincarini, Z Zhao, C Slaney, J Boath, L Furic, C Angel, SM Jane, WA Phillips, SA Stacker, CS Farah, C Darido
Nature Communications | Published : 2023
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 th..
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Awarded by Peter MacCallum Cancer Centre
Funding Acknowledgements
We thank members of the Darido laboratory including Imran Khan, Adelle Marrazzo, Sarah Fourari and Jade Tran for technical and general assistance with experiments and figures. The authors would like to acknowledge the assistance of David Goode from the Computational Cancer Biology Programme at the Peter MacCallum Cancer Centre. We also acknowledge the assistance from the Peter MacCallum Cancer Centre Core Facilities including the Bioinformatics Core Facility, the Victorian Centre for Functional Genomics, the Molecular Genomics Centre, the Centre for Advanced Histology & Microscopy and the Animal Facility. We thank Oliver Bissinger for the intellectual contribution and support of the co-author CG. This research was supported by a grant from the Australian National Health and Medical Research Council (NHMRC, APP1106697) to SJM and CD, and a Victorian Cancer Agency mid-career Fellowship (MCRF16017) to CD.