Overexpression of TC-PTP in murine epidermis attenuates skin tumor formation

Authors

Mihwa Kim, The University of Texas Rio Grande Valley
Liza D. Morales, The University of Texas Rio Grande Valley
Cheol Jung Lee, The University of Texas Rio Grande Valley
Serena A. Olivarez, The University of Texas Rio Grande Valley
Woo Jin Kim, The University of Texas Rio Grande Valley
Joselin Hernandez, The University of Texas Rio Grande Valley
Srinivas Mummidi, The University of Texas Rio Grande Valley
Christopher Jenkinson, The University of Texas Rio Grande Valley
Andrew Tsin, The University of Texas Rio Grande Valley
Ik-Soon Jang, Korea Basic Science Institute
Thomas J. Slaga, University of Texas Health Science Center at San Antonio
Dae Joon Kim, The University of Texas Rio Grande ValleyFollow

Document Type

Article

Publication Date

5-2020

Abstract

T-cell protein tyrosine phosphatase (TC-PTP), encoded by Ptpn2, has been shown to function as a tumor suppressor during skin carcinogenesis. In the current study, we generated a novel epidermal-specific TC-PTP-overexpressing (K5HA.Ptpn2) mouse model to show that TC-PTP contributes to the attenuation of chemically induced skin carcinogenesis through the synergistic regulation of STAT1, STAT3, STAT5, and PI3K/AKT signaling. We found overexpression of TC-PTP increased epidermal sensitivity to DMBA-induced apoptosis and it decreased TPA-mediated hyperproliferation, coinciding with reduced epidermal thickness. Inhibition of STAT1, STAT3, STAT5, or AKT reversed the effects of TC-PTP overexpression on epidermal survival and proliferation. Mice overexpressing TC-PTP in the epidermis developed significantly reduced numbers of tumors during skin carcinogenesis and presented a prolonged latency of tumor initiation. Examination of human papillomas and squamous cell carcinomas (SCCs) revealed that TC-PTP expression was significantly reduced and TC-PTP expression was inversely correlated with the increased grade of SCCs. Our findings demonstrate that TC-PTP is a potential therapeutic target for the prevention of human skin cancer given that it is a major negative regulator of oncogenic signaling.

Comments

© 2020 The Author(s). Original published version available at https://doi.org/10.1038/s41388-020-1282-8

Recommended Citation

Kim, M., Morales, L. D., Lee, C. J., Olivarez, S. A., Kim, W. J., Hernandez, J., Mummidi, S., Jenkinson, C., Tsin, A. T., Jang, I.-S., Slaga, T. J., & Kim, D. J. (2020). Overexpression of TC-PTP in murine epidermis attenuates skin tumor formation. Oncogene, 39(21), 4241–4256. https://doi.org/10.1038/s41388-020-1282-8

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.

Publication Title

Oncogene

DOI

10.1038/s41388-020-1282-8

Academic Level

faculty

Mentor/PI Department

Immunology and Microbiology