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Article

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

  • Authors:
    • Saumya S. Srivastava
    • Hunain Alam
    • Sonam J. Patil
    • Rashmi Shrinivasan
    • Sweta Raikundalia
    • Pratik Rajeev Chaudhari
    • Milind M. Vaidya
  • View Affiliations / Copyright

    Affiliations: Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC), Kharghar, Navi Mumbai, Raigad, Maharashtra 410210, India, Department of Molecular and Cellular Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA
  • Pages: 2393-2401
    |
    Published online on: March 6, 2018
       https://doi.org/10.3892/or.2018.6298
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Srivastava SS, Alam H, Patil SJ, Shrinivasan R, Raikundalia S, Chaudhari PR and Vaidya MM: Keratin 5/14‑mediated cell differentiation and transformation are regulated by TAp63 and Notch‑1 in oral squamous cell carcinoma‑derived cells. Oncol Rep 39: 2393-2401, 2018.
APA
Srivastava, S.S., Alam, H., Patil, S.J., Shrinivasan, R., Raikundalia, S., Chaudhari, P.R., & Vaidya, M.M. (2018). Keratin 5/14‑mediated cell differentiation and transformation are regulated by TAp63 and Notch‑1 in oral squamous cell carcinoma‑derived cells. Oncology Reports, 39, 2393-2401. https://doi.org/10.3892/or.2018.6298
MLA
Srivastava, S. S., Alam, H., Patil, S. J., Shrinivasan, R., Raikundalia, S., Chaudhari, P. R., Vaidya, M. M."Keratin 5/14‑mediated cell differentiation and transformation are regulated by TAp63 and Notch‑1 in oral squamous cell carcinoma‑derived cells". Oncology Reports 39.5 (2018): 2393-2401.
Chicago
Srivastava, S. S., Alam, H., Patil, S. J., Shrinivasan, R., Raikundalia, S., Chaudhari, P. R., Vaidya, M. M."Keratin 5/14‑mediated cell differentiation and transformation are regulated by TAp63 and Notch‑1 in oral squamous cell carcinoma‑derived cells". Oncology Reports 39, no. 5 (2018): 2393-2401. https://doi.org/10.3892/or.2018.6298
Copy and paste a formatted citation
x
Spandidos Publications style
Srivastava SS, Alam H, Patil SJ, Shrinivasan R, Raikundalia S, Chaudhari PR and Vaidya MM: Keratin 5/14‑mediated cell differentiation and transformation are regulated by TAp63 and Notch‑1 in oral squamous cell carcinoma‑derived cells. Oncol Rep 39: 2393-2401, 2018.
APA
Srivastava, S.S., Alam, H., Patil, S.J., Shrinivasan, R., Raikundalia, S., Chaudhari, P.R., & Vaidya, M.M. (2018). Keratin 5/14‑mediated cell differentiation and transformation are regulated by TAp63 and Notch‑1 in oral squamous cell carcinoma‑derived cells. Oncology Reports, 39, 2393-2401. https://doi.org/10.3892/or.2018.6298
MLA
Srivastava, S. S., Alam, H., Patil, S. J., Shrinivasan, R., Raikundalia, S., Chaudhari, P. R., Vaidya, M. M."Keratin 5/14‑mediated cell differentiation and transformation are regulated by TAp63 and Notch‑1 in oral squamous cell carcinoma‑derived cells". Oncology Reports 39.5 (2018): 2393-2401.
Chicago
Srivastava, S. S., Alam, H., Patil, S. J., Shrinivasan, R., Raikundalia, S., Chaudhari, P. R., Vaidya, M. M."Keratin 5/14‑mediated cell differentiation and transformation are regulated by TAp63 and Notch‑1 in oral squamous cell carcinoma‑derived cells". Oncology Reports 39, no. 5 (2018): 2393-2401. https://doi.org/10.3892/or.2018.6298
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