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

Mihwa Kim, Liza D. Morales, Cheol Jung Lee, Serena A. Olivarez, Woo Jin Kim, Joselin Hernandez, Srinivas Mummidi, Christopher P Jenkinson, Andrew T. Tsin, Ik Soon Jang, Thomas J. Slaga, Dae Joon Kim

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)4241-4256
Number of pages16
JournalOncogene
Volume39
Issue number21
DOIs
StatePublished - May 21 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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