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TPL2 Is an Oncogenic Driver in Keratocanthoma and Squamous Cell Carcinoma
Cited 21 time in
Web of Science
Cited 21 time in Scopus
- Authors
- Issue Date
- 2016-11
- Publisher
- American Association for Cancer Research
- Citation
- Cancer Research, Vol.76 No.22, pp.6712-6722
- Abstract
- Squamous cell carcinoma (SCC) and keratoacanthoma (KA; SCC/KA) research has been hampered mainly by our lack of understanding the underlying genetic and epigenetic alterations associated with SCC/KA development, as well as the lack of animal models that faithfully recapitulate histopathologic features of human SCC/KA. Here, we show that TPL2 overexpression induced both cell transformation in immortalized human keratinocytes and SCC and KA-like cutaneous SCC (cSCC) development in mice. Mechanistically, activation of TPL2 downstream signaling pathways such as MEK/ERK MAPK, mTOR, NF-kB, and p38 MAPK leads to TPL2-mediated cell transformation in immortalized human keratinocytes and tumorigenesis in mice. Most importantly, TPL2 overexpression is required for iTPL2 TG-driven SCC and KA-like cSCC tumor maintenance, validating TPL2 as a possible drug target for the treatment of SCC/KA. Finally, we verified that TPL2 is overexpressed in human cutaneous metastatic SCC and KA clinical specimens compared with normal skin. Taken together, our results establish TPL2 as an oncogenic driver in SCC/KA development.
- ISSN
- 0008-5472
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