Research Spotlight

Emergence of hybrid states of stem-like cancer cells correlates with poor prognosis in oral cancer. iScience. / Apr 27, 2022

Vipparthi K, Hari K, Chakraborty P, Ghosh S, Patel AK, Ghosh A, Biswas NK, Sharan R, Arun P, Jolly MK, Singh S; 25(5):104317.
doi:10.1016/j.isci.2022.104317; PMID:35602941; PMCID: PMC9114525

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.