alexa P63, A Master Regulator of Epithelial Cancer and a Squamous Cell Carcinoma Driver | OMICS International
ISSN: 2161-0940
Anatomy & Physiology: Current Research

Like us on:

Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

P63, A Master Regulator of Epithelial Cancer and a Squamous Cell Carcinoma Driver

Rokudai S*, Erkhem-Ochir B and Nishiyama M

Department of Molecular Pharmacology and Oncology, Graduate School of Medicine, Gunma University, 3-39-22 Showa, Maebashi, Gunma 371-8511, Japan

*Corresponding Author:
Rokudai S
Department of Molecular Pharmacology and Oncology
Graduate School of Medicine, Gunma University, 3-39-22 Showa
Maebashi, Gunma 371-8511, Japan
Tel: +81-27-220-7962
E-mail: [email protected]

Received date: August 21, 2017; Accepted date: August 31, 2017; Published date: September 07, 2017

Citation: Rokudai S, Erkhem-Ochir B, Nishiyama M (2017) P63, A Master Regulator of Epithelial Cancer and a Squamous Cell Carcinoma Driver. Anat Physiol 7:281. doi: 10.4172/2161-0940.1000281

Copyright: © 2017 Rokudai S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Anatomy & Physiology: Current Research


TP63; TP53; PDGFRα; STXBP4; Squamous cell carcinoma (SCC)


Non-small cell lung cancer (NSCLC) accounts for more than 80% of all cases of lung cancer, and is sub-classified mainly into adenocarcinoma (AC) and squamous cell carcinoma (SCC) [1]. Current treatment strategies for NSCLC depend on the histological tumor subtypes and molecular targeted agents for targetable genome alterations. Although there have been significant advances in the treatment of NSCLC, therapeutic improvements in the treatment of lung SCC have lagged behind for AC, and further prognostic progresses are needed to enable identification of SCC specific molecules or genomic alterations that could be beneficial for biomarkers and therapeutic targets [2]. While several immunohistochemical markers have been improved for their utility in distinguishing lung SCC from lung AC, the ΔNp63 (p40) is a highly specific marker for lung SCC [3-5].

p63, a member of the p53 family, has significant homology with p53 and regulates crucial events in the proliferative potential of epithelial stem cells and the normal epidermal stratification development [6]. Alternative splicing of the TP63 gene generates transcripts encoding two opposing functions of isoforms with the transactivation domain (TAp63) and without the domain (ΔNp63) [7-9]. The splicing at the 3’ end of p63, resulting in the isoforms α, β and γ [7,9,10]. Early studies showed that ΔNp63 acts as a dominant-negative transcriptional repressor to inhibit p53- or p63-mediated transcription in vitro and in vivo, consistent with a potential oncogenic role for the ΔNp63 isoform [8,11]. However, the ΔNp63 isoform also has transcriptional activity that is independent of the second transactivation domain [12]. Although TAp63 and ΔNp63 shows overlapping distributions in some epithelial tissues, ΔNp63 is more expressed in basal cells, suggesting that single expression of ΔNp63 is correlated with the cancer stem-like cell populations and that the distinct patterns of p63 isoforms may contribute to epithelial proliferation and differentiation [13,14].

The genomic regions of the p63 gene are frequently amplified and the levels of p63 are sometimes altered in a variety of epithelial cancers, including lung SCC, head and neck SCC, bladder cancer, breast cancer and cervical cancer [4,13,15,16]. Although the genomic region containing the TP63 gene is frequently amplified in SCCs, the expression levels of p63 are also regulated by ubiquitin-mediated proteolysis by E3 ubiquitin ligases, such as Nedd4 [17], Itch [18], FBW7 [19] and Pirh2 [20]. The levels of ΔNp63 proteins are also regulated in a coordinated manner by two scaffold proteins, Syntaxin Binding Protein 4 (STXBP4) and Receptor of activated kinase C1 (RACK1), which directly interact with ΔNp63 [21,22].

Newly reported that STXBP4 plays a positive regulator of ΔNp63 stability for enhanced oncogenic potential through Platelet-Derived Growth Factor Receptor α (PDGFRα) signaling in a ΔNp63-dependent manner in lung SCC [21,23], although STXBP4 is originally identified as a glucose transporter [24,25]. In line with this result, the inhibition of the complex formation between p53 and NF-Y by gain-of-function (GOF) of mutant p53 enhances PDGFRβ expression and promotes metastasis in a subset of pancreatic cancers [26]. In addition, an interaction of p63 with mutant p53 regulates the expression of p63 target genes to enhance invasion and metastasis [27]. Hence, the oncogenic activity of mutant p53 may be dependent on the physical association between p63 and mutant p53.

Despite p63, a master regulator of epithelial cells, is regulated by the multiple signaling pathways that could contribute to several epithelial cancers, such as the Wnt, FGFR and EGFR pathways [15,28,29], p63 expression is also reported to be decreased during progression to invasion and metastasis, and the loss of p63 expression is associated with poor prognosis in some cases [29-31]. It could be the balance between the TA isotype as a tumor suppressor and ΔN isotype as an oncogene, as well as the tissue context, which is critical for proliferation and differentiation in both epithelial stem cells and cancer stem cells. These issues highlight the growing importance of accurate identification of SCC treatment for assigning patients to appropriate histology-based therapies and the triage of tissue for appropriate molecular studies.


Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Article Usage

  • Total views: 827
  • [From(publication date):
    September-2017 - Sep 23, 2018]
  • Breakdown by view type
  • HTML page views : 780
  • PDF downloads : 47

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2018-19
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

bornova escort

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals


[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

© 2008- 2018 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
Leave Your Message 24x7