Hishida, TomoakiVazquez-Ferrer, EricHishida Nozaki, YurikoTakemoto, YutoHatanaka, FumiyukiYoshida, KeiPrieto, JavierSahu, Sanjeeb KumarTakahashi, YutaReddy, PradeepO'Keefe, David D.Rodriguez Esteban, ConcepciónKnoepfler, Paul S.Nuñez Delicado, EstrellaCastells Garangou, AntoniCampistol Plana, Josep M.Kato, RyujiNakagawa, HiroshiIzpisúa Belmonte, Juan Carlos2023-02-282023-02-282022-03-042296-634Xhttps://hdl.handle.net/2445/194308t is widely believed that cellular senescence plays a critical role in both aging and cancer, and that senescence is a fundamental, permanent growth arrest that somatic cells cannot avoid. Here we show that Myc plays an important role in self-renewal of esophageal epithelial cells, contributing to their resistance to cellular senescence. Myc is homogeneously expressed in basal cells of the esophageal epithelium and Myc positively regulates their self-renewal by maintaining their undifferentiated state. Indeed, Myc knockout induced a loss of the undifferentiated state of esophageal epithelial cells resulting in cellular senescence while forced MYC expression promoted oncogenic cell proliferation. A superoxide scavenger counteracted Myc knockout induced senescence, therefore suggesting that a mitochondrial superoxide takes part in inducing senescence. Taken together, these analyses reveal extremely low levels of cellular senescence and senescence-associated phenotypes in the esophageal epithelium, as well as a critical role for Myc in self-renewal of basal cells in this organ. This provides new avenues for studying and understanding the links between stemness and resistance to cellular senescence.11 p.application/pdfengcc-by (c) Hishida, Tomoaki et al., 2022https://creativecommons.org/licenses/by/4.0/CàncerEnvellimentMitocondrisCancerAgingMitochondriainfo:eu-repo/semantics/article7252822023-02-28info:eu-repo/semantics/openAccess9300895