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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1427663

USP7 regulates growth and maintains the stemness of p53-mutant colorectal cancer cells via stabilizing of mutant p53

Provisionally accepted
Xue Li Xue Li *Jie Pan Jie Pan Pengcheng Zheng Pengcheng Zheng
  • The First People’s Hospital of Yunnan Province, Kunming, China

The final, formatted version of the article will be published soon.

    TP53 is one of the most frequently mutated genes among all cancers, and TP53 mutants occur more than 40% in colorectal cancers (CRCs). Accumulation of mutant p53 may augment colorectal cancer stem cells (CCSCs) phenotype and enhance colorectal tumorigenesis. Thus, reducing the level of mutant p53 protein is an attractive anticancer strategy. In this study, we found that USP7 and mutant p53 were dramatically elevated in CSC-enriched colorectal cancer cells and USP7 expression was positively associated with self-renewal and maintenance of CCSCs. USP7 regulated cell growth, stemness and migration of colorectal cancer cells. USP7 depletion significantly reduced proliferation of cancer cells and suppressed the self-renewal of CSC-enriched colorectal cancer cells. Further studies indicated that USP7 knockdown could significantly decrease mutant p53 protein levels both in CRCs and CSC-enriched colorectal cancer cells. Moreover, mutant p53 was stabilized by USP7 and they interacted with each other. Furthermore, USP7 inhibitor P5091 also diminished CCSCs self-renewal and reduced mutant p53 levels. Taken together, our findings demonstrated that USP7 involved in the modulation of CCSCs stemness，as well as a critical target for clinical treatment of cancers with different p53 mutations.

    Keywords: USP7, Stemness, mutant p53, P5091, colorectal cancer, antitumor

    Received: 31 May 2024; Accepted: 16 Aug 2024.

    Copyright: © 2024 Li, Pan and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xue Li, The First People’s Hospital of Yunnan Province, Kunming, China

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