Myc Supports Self-Renewal of Basal Cells in the Esophageal Epithelium

Autor: Tomoaki Hishida, Eric Vazquez-Ferrer, Yuriko Hishida-Nozaki, Yuto Takemoto, Fumiyuki Hatanaka, Kei Yoshida, Javier Prieto, Sanjeeb Kumar Sahu, Yuta Takahashi, Pradeep Reddy, David D. O’Keefe, Concepcion Rodriguez Esteban, Paul S. Knoepfler, Estrella Nuñez Delicado, Antoni Castells, Josep M. Campistol, Ryuji Kato, Hiroshi Nakagawa, Juan Carlos Izpisua Belmonte
Rok vydání: 2021
Předmět:
Zdroj: Frontiers in cell and developmental biology. 10
ISSN: 2296-634X
Popis: It 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.
Databáze: OpenAIRE