%0 Journal Article
%A Paul, Mariel C
%A Schneeweis, Christian
%A Falcomatà, Chiara
%A Shan, Chuan
%A Rossmeisl, Daniel
%A Koutsouli, Stella
%A Klement, Christine
%A Zukowska, Magdalena
%A Widholz, Sebastian
%A Jesinghaus, Moritz
%A Heuermann, Konstanze K
%A Engleitner, Thomas
%A Seidler, Barbara
%A Sleiman, Katia
%A Steiger, Katja
%A Tschurtschenthaler, Markus
%A Walter, Benjamin
%A Weidemann, Sören A
%A Pietsch, Regina
%A Schnieke, Angelika
%A Schmid, Roland M
%A Robles, Maria S
%A Andrieux, Geoffroy
%A Börries, Melanie
%A Rad, Roland
%A Schneider, Günter
%A Saur, Dieter Karl Maximilian
%T Non-canonical functions of SNAIL drive context-specific cancer progression.
%J Nature Communications
%V 14
%N 1
%@ 2041-1723
%C [London]
%I Nature Publishing Group UK
%M DKFZ-2023-00462
%P 1201
%D 2023
%X 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 p16INK4A-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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:36882420
%R 10.1038/s41467-023-36505-0
%U https://inrepo02.dkfz.de/record/274160