SUPT5H Depletion Suppresses EMT via p53/Rb Pathway

SUPT5H/SPT5, a universally conserved transcription factor across three domains of life, has been linked to promoter-proximal pausing, and its oncogenic role in cancer progression has been well-documented in several cancer types. In this study, we report CRISPR-Cas9-based SUPT5H knockdown-induced senescence as a potential cancer therapy for the first time. The knockdown of SUPT5H triggers the DNA damage-inducing p53 and Rb axes of senescence, leading to the upregulation of cell cycle inhibitors such as p21 and p27 resulting in inhibition of cell cycle progression proteins CDK4/6, as well as Cyclin D, E and A, thus resulting in senescence. Senescence induction results in the suppression of epithelial to mesenchymal transition via the upregulation of E-Cadherin and the downregulation of vimentin. Furthermore, the induction of senescence also leads to the suppression of immune evasion, offering a ray of hope in the fight against cancer.