Non-canonical functions of SNAIL drive context-specific cancer progression
2023 | journal article. A publication with affiliation to the University of Göttingen.
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Non-canonical functions of SNAIL drive context-specific cancer progression
Paul, M. C.; Schneeweis, C.; Falcomatà, C.; Shan, C.; Rossmeisl, D.; Koutsouli, S. & Klement, C. et al. (2023)
Nature Communications, 14(1). DOI: https://doi.org/10.1038/s41467-023-36505-0
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Details
- Authors
- Paul, Mariel C.; Schneeweis, Christian; Falcomatà, Chiara; Shan, Chuan; Rossmeisl, Daniel; Koutsouli, Stella; Klement, Christine; Zukowska, Magdalena; Widholz, Sebastian A.; Jesinghaus, Moritz; Saur, Dieter
- Abstract
- Abstract SNAIL is a key transcriptional regulator in embryonic development and cancer. Its effects in physiology and disease are believed to be linked to its role as a master regulator of epithelial-to-mesenchymal transition (EMT). Here, we report EMT-independent oncogenic SNAIL functions in cancer. Using genetic models, we systematically interrogated SNAIL effects in various oncogenic backgrounds and tissue types. SNAIL-related phenotypes displayed remarkable tissue- and genetic context-dependencies, ranging from protective effects as observed in KRAS- or WNT-driven intestinal cancers, to dramatic acceleration of tumorigenesis, as shown in KRAS-induced pancreatic cancer. Unexpectedly, SNAIL-driven oncogenesis was not associated with E-cadherin downregulation or induction of an overt EMT program. Instead, we show that SNAIL induces bypass of senescence and cell cycle progression through p16 INK4A -independent inactivation of the Retinoblastoma (RB)-restriction checkpoint. Collectively, our work identifies non-canonical EMT-independent functions of SNAIL and unravel its complex context-dependent role in cancer.
- Issue Date
- 2023
- Journal
- Nature Communications
- eISSN
- 2041-1723
- Language
- English