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Medientyp:
E-Artikel
Titel:
Genetic dissection of colorectal cancer progression by orthotopic transplantation of engineered cancer organoids
Beteiligte:
Fumagalli, Arianna;
Drost, Jarno;
Suijkerbuijk, Saskia J. E.;
van Boxtel, Ruben;
de Ligt, Joep;
Offerhaus, G. Johan;
Begthel, Harry;
Beerling, Evelyne;
Tan, Ee Hong;
Sansom, Owen J.;
Cuppen, Edwin;
Clevers, Hans;
van Rheenen, Jacco
Erschienen:
Proceedings of the National Academy of Sciences, 2017
Erschienen in:
Proceedings of the National Academy of Sciences, 114 (2017) 12
Sprache:
Englisch
DOI:
10.1073/pnas.1701219114
ISSN:
0027-8424;
1091-6490
Entstehung:
Anmerkungen:
Beschreibung:
Significance Metastasis is the main cause of cancer death, but the underlying mechanisms are largely unknown. Here, we developed an orthotopic organoid transplantation approach and used engineered human colon tumor organoids to study the contribution of common CRC mutations to metastasis. Using this approach, we show that the combination of oncogenic mutations in Wnt, EGFR, P53, and TGF-β signaling pathways facilitates efficient tumor cell migration and metastasis. These mutations allow growth independent of stem cell niche factors, enabling cells to grow at foreign distant sites that lack these factors. Our findings suggest that metastasis is a direct consequence of acquired niche independency.