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• W3017292653 endingPage "e201900601" @default.
• W3017292653 startingPage "e201900601" @default.
• W3017292653 abstract "Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer characterized by increased mortality. Here, we show for the first time that anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase of the insulin receptor superfamily, plays a pivotal role in the pathogenesis of cSCC. Our data demonstrate that the overexpression of the constitutively active, mutated ALK, ALK F1174L , is sufficient to initiate the development of cSCC and is 100% penetrant. Moreover, we show that cSCC development upon ALK F1174L overexpression is independent of the cell-of-origin. Molecularly, our data demonstrate that ALK F1174L cooperates with oncogenic Kras G12D and loss of p53 , well-established events in the biology of cSCC. This cooperation results in a more aggressive cSCC type associated with a higher grade histological morphology. Finally, we demonstrate that Stat3 is a key downstream effector of ALK F1174L and likely plays a role in ALK F1174L -driven cSCC tumorigenesis. In sum, these findings reveal that ALK can exert its tumorigenic potential via cooperation with multiple pathways crucial in the pathogenesis of cSCC. Finally, we show that human cSCCs contain mutations in the ALK gene. Taken together, our data identify ALK as a new key player in the pathogenesis of cSCC, and this knowledge suggests that oncogenic ALK signaling can be a target for future clinical trials." @default.
• W3017292653 created "2020-04-24" @default.
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• W3017292653 date "2020-04-20" @default.
• W3017292653 modified "2023-10-10" @default.
• W3017292653 title "Oncogenic <i>ALK</i>^{<i>F1174L</i>} drives tumorigenesis in cutaneous squamous cell carcinoma" @default.
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• W3017292653 doi "https://doi.org/10.26508/lsa.201900601" @default.
• W3017292653 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7184028" @default.
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• W3017292653 hasPublicationYear "2020" @default.
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