| First Author | Lee JH | Year | 2016 |
| Journal | Cancer Res | Volume | 76 |
| Issue | 22 | Pages | 6712-6722 |
| PubMed ID | 27503930 | Mgi Jnum | J:237840 |
| Mgi Id | MGI:5817272 | Doi | 10.1158/0008-5472.CAN-15-3274 |
| Citation | Lee JH, et al. (2016) TPL2 Is an Oncogenic Driver in Keratocanthoma and Squamous Cell Carcinoma. Cancer Res 76(22):6712-6722 |
| abstractText | 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-kappaB, 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. (c)2016 AACR. |
