Keratin 5/14‑mediated cell differentiation and transformation are regulated by TAp63 and Notch‑1 in oral squamous cell carcinoma‑derived cells

Keratins 5/14 (K5/14) are intermediate filament proteins expressed in the basal layer of stratified epithelial cells and are known targets of p63. Previous research in our laboratory showed that upon K5/14 downregulation in oral squamous cell carcinoma (OSCC)‑derived cells, there was an increase in...

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Bibliographic Details
Published in:	Oncology reports Vol. 39; no. 5; pp. 2393 - 2401
Main Authors:	Srivastava, Saumya S, Alam, Hunain, Patil, Sonam J, Shrinivasan, Rashmi, Raikundalia, Sweta, Chaudhari, Pratik Rajeev, Vaidya, Milind M
Format:	Journal Article
Language:	English
Published:	Greece Spandidos Publications 01-05-2018 Spandidos Publications UK Ltd
Subjects:	Care and treatment Cellular proteins Cloning Colorectal cancer Development and progression Gene expression Genetic aspects Health aspects Keratin Medical research Motility Mouth cancer Oral cancer Plasmids Proteins Squamous cell carcinoma Studies Tumorigenesis United States > US India
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Summary:	Keratins 5/14 (K5/14) are intermediate filament proteins expressed in the basal layer of stratified epithelial cells and are known targets of p63. Previous research in our laboratory showed that upon K5/14 downregulation in oral squamous cell carcinoma (OSCC)‑derived cells, there was an increase in intracellular Notch‑1 levels and differentiation markers such as involucrin, keratin 1 and a decrease in tumorigenic potential in vivo. However, the molecules involved in the K14 regulated cell differentiation and transformation are not known to date. In order to understand the possible role of TAp63, we downregulated TAp63 in a K14‑knockdown background. We observed that there was a decrease in the expression of Notch‑1. Expression levels of differentiation markers such as involucrin, K1, loricrin and filaggrin were also decreased. Furthermore, TAp63 downregulation led to an increase in invasion, migration and in vivo tumorigenic potential of these cells. We observed a decrease in β‑catenin signaling in K14‑downregulated cells. Notably, when TAp63 was downregulated in K14‑knockdown cells, there was increase in non‑phospho β‑catenin levels. Hence, this study indicates that TAp63 plays an important role in K14‑downregulated cells possibly by regulating the Notch‑1 expression. K14 regulates the expression of TAp63 which in turn regulates expression of Notch‑1. The present study is a step forward in our quest to understand the functional significance of molecules that regulate the process of differentiation and tumorigenesis in stratified epithelial cells.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1021-335X 1791-2431
DOI:	10.3892/or.2018.6298