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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-04-14

AUTHORS

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

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. More... »

PAGES

4241-4256

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41388-020-1282-8

DOI

http://dx.doi.org/10.1038/s41388-020-1282-8

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32286519


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48 apoptosis
49 attenuation
50 cancer
51 carcinogenesis
52 carcinoma
53 cell carcinoma
54 cell protein tyrosine phosphatase
55 contributes
56 current study
57 effect
58 epidermal sensitivity
59 epidermal survival
60 epidermal thickness
61 epidermis
62 examination
63 expression
64 findings
65 formation
66 grade
67 grade of SCC
68 human papilloma
69 human skin cancer
70 hyperproliferation
71 inhibition
72 inhibition of STAT1
73 initiation
74 latency
75 major negative regulator
76 mice
77 model
78 mouse model
79 murine epidermis
80 negative regulator
81 number
82 number of tumors
83 oncogenic signaling
84 overexpression
85 papillomas
86 phosphatase
87 potential therapeutic target
88 prevention
89 proliferation
90 prolonged latency
91 protein tyrosine phosphatase
92 reduced epidermal thickness
93 regulation
94 regulator
95 sensitivity
96 signaling
97 skin cancer
98 skin carcinogenesis
99 skin tumor formation
100 squamous cell carcinoma
101 study
102 suppressor
103 survival
104 synergistic regulation
105 target
106 therapeutic target
107 thickness
108 tumor formation
109 tumor initiation
110 tumor suppressor
111 tumors
112 tyrosine phosphatase
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