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

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 high throughputsequencing were performed to explore the underlying molecular mechanisms. The RNA sequencing analysis of head and neck cancer (HNC) cell lines SCC15 and SCC25 upon YBX1 knockout. The RNA sequencing analysis of normal oral cells (OKF6) and HNC cells (SCC15 and SCC25).