TY - JOUR
T1 - p53 signaling in cancer progression and therapy
AU - Marei, Hany E.
AU - Althani, Asmaa
AU - Afifi, Nahla
AU - Hasan, Anwarul
AU - Caceci, Thomas
AU - Pozzoli, Giacomo
AU - Morrione, Andrea
AU - Giordano, Antonio
AU - Cenciarelli, Carlo
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Cancer progression
KW - Cancer therapy
KW - Tumor suppressor gene
KW - p53 signaling
KW - Gain of function mutation
KW - Cancer progression
KW - Cancer therapy
KW - Tumor suppressor gene
KW - p53 signaling
KW - Gain of function mutation
UR - http://hdl.handle.net/10807/233388
U2 - 10.1186/s12935-021-02396-8
DO - 10.1186/s12935-021-02396-8
M3 - Article
SN - 1475-2867
VL - 21
SP - 703
EP - 717
JO - Cancer Cell International
JF - Cancer Cell International
ER -