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-κB, 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. Cancer Res; 76(22); 6712-22. ©2016 AACR.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Lee JH,Lee JH,Lee SH,Do SI,Cho SD,Forslund O,Inn KS,Lee JS,Deng FM,Melamed J,Jung JU,Jeong JHdoi
10.1158/0008-5472.CAN-15-3274subject
Has Abstractpub_date
2016-11-15 00:00:00pages
6712-6722issue
22eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-15-3274journal_volume
76pub_type
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