Molecular Mechanisms of p63-Mediated Squamous Cancer Pathogenesis
Michael A Moses1, Andrea L George1, Nozomi Sakakibara1
1Laboratory of Molecular Oncology, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
International Journal of Molecular Sciences
|July 26, 2019
Summary
The p63 gene, specifically the ΔNp63α isoform, is crucial for skin development and homeostasis. Its dysregulation contributes to squamous cell cancers by promoting proliferation and blocking differentiation.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cancer Biology
Background:
- p63 is a transcription factor vital for squamous epithelium development and homeostasis.
- ΔNp63α is the main p63 isoform in stratified squamous epithelium and acts as a stem cell marker.
- Overexpression of p63 is observed in various squamous cell cancers.
Purpose of the Study:
- To review the role of ΔNp63α in normal epidermal biology.
- To explore how ΔNp63α dysregulation contributes to cutaneous squamous cancer development.
- To integrate knowledge from other organ site cancers with p63 overexpression.
Main Methods:
- Literature review focusing on p63's role in skin biology and cancer.
- Analysis of studies on ΔNp63α function in epidermal homeostasis.
- Examination of p63's involvement in cancer pathogenesis, including proliferation, differentiation, apoptosis, senescence, adhesion, and migration.
Main Results:
- ΔNp63α directs lineage commitment in the epidermis and influences proliferation, survival, and terminal differentiation.
- Dysregulation of ΔNp63α impacts epidermal homeostasis and contributes to cancer by inhibiting apoptosis and senescence.
- Overexpressed ΔNp63α can alter the tumor microenvironment via matrix remodeling, angiogenesis, and immune cell recruitment.
Conclusions:
- ΔNp63α plays a significant role in normal epidermal biology and stem cell function.
- Aberrant ΔNp63α expression is a key driver in the development of cutaneous squamous cell carcinoma.
- Understanding ΔNp63α's functions provides insights into squamous cancer pathogenesis across multiple organ sites.
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