Publication details

Noncanonical roles of p53 in cancer stemness and their implications in sarcomas

Authors

CURYLOVÁ Lucie RAMOS Helena SARAIVA Lucília ŠKODA Jan

Year of publication 2022
Type Article in Periodical
Magazine / Source Cancer letters
MU Faculty or unit

Faculty of Science

Citation
Web https://www.sciencedirect.com/science/article/pii/S030438352100553X?via%3Dihub
Doi http://dx.doi.org/10.1016/j.canlet.2021.10.037
Keywords p53; Sarcoma; Mesenchymal stem cells; Cancer stem cells; p53-targeted therapy
Description Impairment of the prominent tumor suppressor p53, well known for its canonical role as the "guardian of the genome", is found in almost half of human cancers. More recently, p53 has been suggested to be a crucial regulator of stemness, orchestrating the differentiation of embryonal and adult stem cells, suppressing reprogramming into induced pluripotent stem cells, or inhibiting cancer stemness (i.e., cancer stem cells, CSCs), which underlies the development of therapy-resistant tumors. This review addresses these noncanonical roles of p53 and their implications in sarcoma initiation and progression. Indeed, dysregulation of p53 family proteins is a common event in sarcomas and is associated with poor survival. Additionally, emerging studies have demonstrated that loss of wild-type p53 activity hinders the terminal differentiation of mesenchymal stem cells and leads to the development of aggressive sarcomas. This review summarizes recent findings on the roles of aberrant p53 in sarcoma development and stemness and further describes therapeutic approaches to restore normal p53 activity as a promising anti-CSC strategy to treat refractory sarcomas.
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