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

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 revealed an epithelial-mesenchymal transition (EMT) signature within the epithelial cancer-cell population. The EMT signature coincided with PI3K/mTOR inactivation in the mesenchymal subtype. Conversely, the signature was suppressed in epithelial cells of the basal subtype which exhibits hyperactive PI3K/mTOR signalling. We further identified YBX1 phosphorylation, downstream of the PI3K/mTOR pathway, restrains 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, emerged as a prognostic marker for overall patient outcomes. Expression profiling by reverse-phase protein array were performed to explore the underlying molecular mechanisms. The reverse-phase protein array analysis of head and neck cancer (HNC) cell lines SCC15 and SCC25 upon YBX1 knockout. The reverse-phase protein array analysis of normal oral cells (OKF6) and HNC cells (SCC15 and SCC25). The reverse-phase protein array analysis of mouse tissues (wildtype, Grhl3cKO, Pik3ca, Pik3caGrhl3cKO tumours and adjacent tissues)