Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 May 31;20(11):2683.
doi: 10.3390/ijms20112683.

p63 at the Crossroads between Stemness and Metastasis in Breast Cancer

Veronica Gatti  1 , Lucilla Bongiorno-Borbone  2 , Claudia Fierro  3 , Margherita Annicchiarico-Petruzzelli  4 , Gerry Melino  5   6 , Angelo Peschiaroli  7
Affiliations
Review

p63 at the Crossroads between Stemness and Metastasis in Breast Cancer

Veronica Gatti et al. Int J Mol Sci. .

Abstract

After lung cancer, breast cancer (BC) is the most frequent cause of cancer death among women, worldwide. Although advances in screening approaches and targeted therapeutic agents have decreased BC incidence and mortality, over the past five years, triple-negative breast cancer (TNBC) remains the breast cancer subtype that displays the worst prognosis, mainly due to the lack of clinically actionable targets. Genetic and molecular profiling has unveiled the high intrinsic heterogeneity of TNBC, with the basal-like molecular subtypes representing the most diffuse TNBC subtypes, characterized by the expression of basal epithelial markers, such as the transcription factor p63. In this review, we will provide a broad picture on the physiological role of p63, in maintaining the basal epithelial identity, as well as its involvement in breast cancer progression, emphasizing its relevance in tumor cell invasion and stemness.

Keywords: TNBC; cancer stem cell; epithelial tumors; metastasis; p53 family.

PubMed Disclaimer

Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Schematic model showing the molecular heterogeneity of triple-negative breast cancer (TNBC). Based on the expression profile, TNBC can be classified into distinct subtypes— Basal-like 1 (BL1), basal-like 2 (BL2), immune modulatory (IM), mesenchymal (M), mesenchymal stem–like (MSL), and luminal androgen receptor (LAR). The percentage of each subtypes is also indicated.
Figure 2
Figure 2
The TP63 gene architecture. TP63 gene encodes several proteins, thanks to two distinct promoters (P1 and P2) and differential splicing events at the 3′ end of its RNA (see text for details).
Figure 3
Figure 3
Schematic model of ΔNp63 physiological role in mammary gland. (A) Representation of mature mammary gland duct showing an inner layer of luminal cells surrounded by a network of basal myoepithelial cells and scattered stem cells. (B) Magnification of the inter- and intra-cellular signaling pathways orchestrated by ΔNp63, aimed at preserving the stem cell self-renewal potential, as well as determining the luminal or basal fate.
Figure 4
Figure 4
Schematic model of p63-dependent routes involved in breast tumor progression (see text for details).
See this image and copyright information in PMC

References

    1. DeSantis C.E., Ma J., Goding Sauer A., Newman L.A., Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA A Cancer J. Clin. 2017;67:439–448. doi: 10.3322/caac.21412. - DOI - PubMed
    1. Abubakar I.I., Tillmann T., Banerjee A. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;385:117–171. - PMC - PubMed
    1. Anderson W.F., Katki H.A., Rosenberg P.S. Incidence of breast cancer in the United States: Current and future trends. J. Natl. Cancer Inst. 2011;103:1397–1402. doi: 10.1093/jnci/djr257. - DOI - PMC - PubMed
    1. Sledge G.W., Mamounas E.P., Hortobagyi G.N., Burstein H.J., Goodwin P.J., Wolff A.C. Past, present, and future challenges in breast cancer treatment. J. Clin. Oncol. 2014;32:1979–1986. doi: 10.1200/JCO.2014.55.4139. - DOI - PMC - PubMed
    1. The Cancer Genome Atlas Network Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61–70. doi: 10.1038/nature11412. - DOI - PMC - PubMed

MeSH terms