Emergence of hybrid states of stem-like cancer cells correlates with poor prognosis in oral cancer
Kavya Vipparthi, Kishore Hari, Priyanka Chakraborty, Subhashis Ghosh, Ankit Kumar Patel, Arnab Ghosh, Nidhan K. Biswas, Rajeev Sharan, Pattatheyil Arun, Mohit Kumar Jolly, Sandeep Singh
Abstract
Cancer cell state transitions emerged as powerful mechanisms responsible for drug tolerance and overall poor prognosis; however, evidences were largely missing in oral cancer. Here, by multiplexing phenotypic markers of stem-like cancer cells (SLCCs); CD44, CD24 and aldehyde dehydrogenase (ALDH), we characterized diversity among multiple oral tumor tissues and cell lines. Two distinct patterns of spontaneous transitions with stochastic bidirectional interconversions on 'ALDH-axis', and unidirectional non-interconvertible transitions on 'CD24-axis' were observed. Interestingly, plastic 'ALDH-axis' was harnessed by cells to adapt to a Cisplatin tolerant state. Furthermore, phenotype-specific RNA sequencing suggested the possible maintenance of intermediate hybrid cell states maintaining stemness within the differentiating subpopulations. Importantly, survival analysis with subpopulation-specific gene sets strongly suggested that cell-state transitions may drive non-genetic heterogeneity, resulting in poor prognosis. Therefore, we have described the phenotypic-composition of heterogeneous subpopulations critical for global tumor behavior in oral cancer; which may provide prerequisite knowledge for treatment strategies.