p53 signaling in cancer progression and therapy

Cancer Cell International

Asmaa Althani¹  Thomas Caceci²  Hany E. Marei³  Anwarul Hasan⁴  Carlo Cenciarelli⁵  Giacomo Pozzoli⁶  Nahla Afifi⁷  Andrea Morrione⁸  Antonio Giordano⁹ 

[1]Biomedical Research Center, Qatar University, Doha, Qatar

[2]Biomedical Sciences, Virginia Maryland College of Veterinary Medicine, Blacksburg, VA, USA

[3]Department of Cytology and Histology, Faculty of Veterinary Medicine, Mansoura University, 35116, Mansoura, Egypt

[4]Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha, Qatar

[5]Institute of Translational Pharmacology-CNR, Rome, Italy

[6]Pharmacology Unit, Fondazione Policlinico A. Gemelli, IRCCS, Rome, Italy

[7]Qatar Biobank, Doha, Qatar

[8]Sbarro Institute for Cancer Research and Molecular Medicine. Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA

[9]Sbarro Institute for Cancer Research and Molecular Medicine. Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA

[10]Department of Medical Biotechnology, University of Siena, Siena, Italy

关键词: p53 signaling;    Tumor suppressor gene;    Gain of function mutation;    Cancer progression;    Cancer therapy;   

DOI  :  10.1186/s12935-021-02396-8

来源: Springer

【 摘 要 】

The p53 protein is a transcription factor known as the "guardian of the genome" because of its critical function in preserving genomic integrity. The TP53 gene is mutated in approximately half of all human malignancies, including those of the breast, colon, lung, liver, prostate, bladder, and skin. When DNA damage occurs, the TP53 gene on human chromosome 17 stops the cell cycle. If p53 protein is mutated, the cell cycle is unrestricted and the damaged DNA is replicated, resulting in uncontrolled cell proliferation and cancer tumours. Tumor-associated p53 mutations are usually associated with phenotypes distinct from those caused by the loss of the tumor-suppressing function exerted by wild-type p53protein. Many of these mutant p53 proteins have oncogenic characteristics, and therefore modulate the ability of cancer cells to proliferate, escape apoptosis, invade and metastasize. Because p53 deficiency is so common in human cancer, this protein is an excellent option for cancer treatment. In this review, we will discuss some of the molecular pathways by which mutant p53 proteins might perform their oncogenic activities, as well as prospective treatment methods based on restoring tumor suppressive p53 functions.

【 授权许可】

CC BY