» Articles » PMID: 36497429

The P53 Family Members P63 and P73 Roles in the Metastatic Dissemination: Interactions with MicroRNAs and TGFβ Pathway

Overview
Journal Cancers (Basel)
Publisher MDPI
Specialty Oncology
Date 2022 Dec 11
PMID 36497429
Authors
Affiliations
Soon will be listed here.
Abstract

TP53 (TP53), p73 (TP73), and p63 (TP63) are members of the p53 transcription factor family, which has many activities spanning from embryonic development through to tumor suppression. The utilization of two promoters and alternative mRNA splicing has been shown to yield numerous isoforms in p53, p63, and p73. TAp73 is thought to mediate apoptosis as a result of nuclear accumulation following chemotherapy-induced DNA damage, according to a number of studies. Overexpression of the nuclear ΔNp63 and ΔNp73 isoforms, on the other hand, suppresses TAp73's pro-apoptotic activity in human malignancies, potentially leading to metastatic spread or inhibition. Another well-known pathway that has been associated to metastatic spread is the TGF pathway. TGFs are a family of structurally related polypeptide growth factors that regulate a variety of cellular functions including cell proliferation, lineage determination, differentiation, motility, adhesion, and cell death, making them significant players in development, homeostasis, and wound repair. Various studies have already identified several interactions between the p53 protein family and the TGFb pathway in the context of tumor growth and metastatic spread, beginning to shed light on this enigmatic intricacy.

Citing Articles

TP63 truncating mutation causes increased cell apoptosis and premature ovarian insufficiency by enhanced transcriptional activation of CLCA2.

Fan Y, Chen S, Chu C, Yin X, Jin J, Zhang L J Ovarian Res. 2024; 17(1):67.

PMID: 38528613 PMC: 10962206. DOI: 10.1186/s13048-024-01396-2.


Epigenetic Landscape and Therapeutic Implication of Gene Isoforms of Doublecortin-Like Kinase 1 for Cancer Stem Cells.

Moore L, Houchen C Int J Mol Sci. 2023; 24(22).

PMID: 38003596 PMC: 10671580. DOI: 10.3390/ijms242216407.


SQLE Knockdown inhibits bladder cancer progression by regulating the PTEN/AKT/GSK3β signaling pathway through P53.

Zou F, Chen W, Song T, Xing J, Zhang Y, Chen K Cancer Cell Int. 2023; 23(1):221.

PMID: 37770925 PMC: 10540347. DOI: 10.1186/s12935-023-02997-5.


p53 and p63 Proteoforms Derived from Alternative Splicing Possess Differential Seroreactivity in Colorectal Cancer with Distinct Diagnostic Ability from the Canonical Proteins.

Montero-Calle A, Garranzo-Asensio M, Torrente-Rodriguez R, Ruiz-Valdepenas Montiel V, Poves C, Dziakova J Cancers (Basel). 2023; 15(7).

PMID: 37046764 PMC: 10092954. DOI: 10.3390/cancers15072102.

References
1.
Moll U, Slade N . p63 and p73: roles in development and tumor formation. Mol Cancer Res. 2004; 2(7):371-86. View

2.
Taylor M, Parvani J, Schiemann W . The pathophysiology of epithelial-mesenchymal transition induced by transforming growth factor-beta in normal and malignant mammary epithelial cells. J Mammary Gland Biol Neoplasia. 2010; 15(2):169-90. PMC: 3721368. DOI: 10.1007/s10911-010-9181-1. View

3.
Shi L, Jackstadt R, Siemens H, Li H, Kirchner T, Hermeking H . p53-induced miR-15a/16-1 and AP4 form a double-negative feedback loop to regulate epithelial-mesenchymal transition and metastasis in colorectal cancer. Cancer Res. 2013; 74(2):532-42. DOI: 10.1158/0008-5472.CAN-13-2203. View

4.
Oft M, Peli J, Rudaz C, Schwarz H, Beug H, Reichmann E . TGF-beta1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev. 1996; 10(19):2462-77. DOI: 10.1101/gad.10.19.2462. View

5.
Muller P, Caswell P, Doyle B, Iwanicki M, Tan E, Karim S . Mutant p53 drives invasion by promoting integrin recycling. Cell. 2010; 139(7):1327-41. DOI: 10.1016/j.cell.2009.11.026. View