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Title: Molecular Mechanisms of p63-Mediated Squamous Cancer Pathogenesis

Abstract

The p63 gene is a member of the p53/p63/p73 family of transcription factors and plays a critical role in development and homeostasis of squamous epithelium. p63 is transcribed as multiple isoforms; ΔNp63α, the predominant p63 isoform in stratified squamous epithelium, is localized to the basal cells and is overexpressed in squamous cell cancers of multiple organ sites, including skin, head and neck, and lung. Further, p63 is considered a stem cell marker, and within the epidermis, ΔNp63α directs lineage commitment. ΔNp63α has been implicated in numerous processes of skin biology that impact normal epidermal homeostasis and can contribute to squamous cancer pathogenesis by supporting proliferation and survival with roles in blocking terminal differentiation, apoptosis, and senescence, and influencing adhesion and migration. ΔNp63α overexpression may also influence the tissue microenvironment through remodeling of the extracellular matrix and vasculature, as well as by enhancing cytokine and chemokine secretion to recruit pro-inflammatory infiltrate. This review focuses on the role of ΔNp63α in normal epidermal biology and how dysregulation can contribute to cutaneous squamous cancer development, drawing from knowledge also gained by squamous cancers from other organ sites that share p63 overexpression as a defining feature.

Authors:
 [1]; ORCiD logo [1];  [1];  [1];  [1];  [1];  [1]
  1. U.S. Food and Drug Administration, Silver Spring, MD (United States). Laboratory of Molecular Oncology, Office of Biotechnology Products, Center for Drug Evaluation and Research
Publication Date:
Research Org.:
Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Office of Science (SC); NCI/FDA Interagency Oncology Task Force (IOTF) Fellowship program; Research Participation Program at the Center for Drug Evaluation and Research; U.S. Food and Drug Administration
OSTI Identifier:
1628384
Grant/Contract Number:  
SC0014664
Resource Type:
Accepted Manuscript
Journal Name:
International Journal of Molecular Sciences (Online)
Additional Journal Information:
Journal Name: International Journal of Molecular Sciences (Online); Journal Volume: 20; Journal Issue: 14; Journal ID: ISSN 1422-0067
Publisher:
MDPI
Country of Publication:
United States
Language:
English
Subject:
Biochemistry & Molecular Biology; Chemistry

Citation Formats

Moses, Michael A., George, Andrea L., Sakakibara, Nozomi, Mahmood, Kanwal, Ponnamperuma, Roshini M., King, Kathryn E., and Weinberg, Wendy C. Molecular Mechanisms of p63-Mediated Squamous Cancer Pathogenesis. United States: N. p., 2019. Web. doi:10.3390/ijms20143590.
Moses, Michael A., George, Andrea L., Sakakibara, Nozomi, Mahmood, Kanwal, Ponnamperuma, Roshini M., King, Kathryn E., & Weinberg, Wendy C. Molecular Mechanisms of p63-Mediated Squamous Cancer Pathogenesis. United States. https://doi.org/10.3390/ijms20143590
Moses, Michael A., George, Andrea L., Sakakibara, Nozomi, Mahmood, Kanwal, Ponnamperuma, Roshini M., King, Kathryn E., and Weinberg, Wendy C. Mon . "Molecular Mechanisms of p63-Mediated Squamous Cancer Pathogenesis". United States. https://doi.org/10.3390/ijms20143590. https://www.osti.gov/servlets/purl/1628384.
@article{osti_1628384,
title = {Molecular Mechanisms of p63-Mediated Squamous Cancer Pathogenesis},
author = {Moses, Michael A. and George, Andrea L. and Sakakibara, Nozomi and Mahmood, Kanwal and Ponnamperuma, Roshini M. and King, Kathryn E. and Weinberg, Wendy C.},
abstractNote = {The p63 gene is a member of the p53/p63/p73 family of transcription factors and plays a critical role in development and homeostasis of squamous epithelium. p63 is transcribed as multiple isoforms; ΔNp63α, the predominant p63 isoform in stratified squamous epithelium, is localized to the basal cells and is overexpressed in squamous cell cancers of multiple organ sites, including skin, head and neck, and lung. Further, p63 is considered a stem cell marker, and within the epidermis, ΔNp63α directs lineage commitment. ΔNp63α has been implicated in numerous processes of skin biology that impact normal epidermal homeostasis and can contribute to squamous cancer pathogenesis by supporting proliferation and survival with roles in blocking terminal differentiation, apoptosis, and senescence, and influencing adhesion and migration. ΔNp63α overexpression may also influence the tissue microenvironment through remodeling of the extracellular matrix and vasculature, as well as by enhancing cytokine and chemokine secretion to recruit pro-inflammatory infiltrate. This review focuses on the role of ΔNp63α in normal epidermal biology and how dysregulation can contribute to cutaneous squamous cancer development, drawing from knowledge also gained by squamous cancers from other organ sites that share p63 overexpression as a defining feature.},
doi = {10.3390/ijms20143590},
journal = {International Journal of Molecular Sciences (Online)},
number = 14,
volume = 20,
place = {United States},
year = {2019},
month = {7}
}

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Works referencing / citing this record:

p63 Is a Promising Marker in the Diagnosis of Unusual Skin Cancer
journal, November 2019

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Molecular Approach to Cutaneous Squamous Cell Carcinoma: From Pathways to Therapy
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ΔNp63 transcript loss in bladder cancer constitutes an independent molecular predictor of TaT1 patients post-treatment relapse and progression
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p63 Is a Promising Marker in the Diagnosis of Unusual Skin Cancer
journal, November 2019

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  • DOI: 10.3390/ijms20225781