Supplemental data from TPL2 Is an Oncogenic Driver in Keratocanthoma and Squamous Cell Carcinoma
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posted on 2023-03-31, 00:24 authored by Jun-Han Lee, Joo-Hyung Lee, Sang Hyuk Lee, Sung-Im Do, Sung-Dae Cho, Ola Forslund, Kyung-Soo Inn, Jeong-Sang Lee, Fang-Ming Deng, Jonathan Melamed, Jae U. Jung, Joseph H. JeongSupplementary Materials and Methods (supplementary information on establsihing cell lines and generating inducible TPL2 transgenic (iTPL2 TG) mice) & Supplementary Figure Legends
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ARTICLE 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.Usage metrics
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