Re-Evaluation of Different Senescent Hallmarks in Therapy-Induced Senescence of Oral Squamous Cell Carcinoma

Cellular senescence is a permanent state of cell cycle arrest, whose role is complicated in cancer development. Identification and isolation of senescent cells is a vital step for further research. However, the non-specificity and variation between senescence types of current senescent markers strongly limit these tasks. The existing ways to identify the other kinds of cellular senescence might be misleading in the field of cancer. In this study, we evaluated the classic methods in a model of chemotherapy-induced senescence in oral squamous cell carcinoma. All the current methods in varying degrees have their flaws. Morphological changes are common among senescent cells, but show the least specificity. The markers, including SA-β-gal, p16, p21, H3K9me3, p-γH2AX and senescence-associated secretory phenotype, are useful to detect senescence. However, these markers show different degrees of false positivity and are disable to isolate viable senescent cells for further study. Even though C 12 FDG staining is a better way to identify and isolate senescent cells with both specificity and sensitivity, absolute purification and dynamic observation of senescent cells are still unattainable. Hence, we tried to construct the p16 INK4a -tdTOMATO model, which might be a new promising way. Funding Information: This work was supported by the National Natural Science Foundation of China (No. 81902768 No.82072995 No.81972544). We have no conflicts of interest. Declaration of Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.