Tripartite interactions between Wnt signaling, Notch and Myb for stem/progenitor cell functions during intestinal tumorigenesis
Markus Germann, Huiling Xu, Jordane Malaterre, Shienny Sampurno, Mathilde Huyghe, Dane Cheasley, Silvia Fre, Robert G Ramsay
STEM CELL RESEARCH | ELSEVIER SCIENCE BV | Published : 2014
Deletion studies confirm Wnt, Notch and Myb transcriptional pathway engagement in intestinal tumorigenesis. Nevertheless, their contrasting and combined roles when activated have not been elucidated. This is important as these pathways are not ablated but rather are aberrantly activated during carcinogenesis. Using ApcMin/+ mice as a source of organoids we documented their transition, on a clone-by-clone basis, to cyst-like spheres with constitutively activated Wnt pathway, increased self-renewal and growth and reduced differentiation. We then looked at this transition when Myb and/or Notch1 are activated. Activated Notch promoted cyst-like organoids. Conversely growth and propagation of cys..View full abstract
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Awarded by NHMRC
We would like to thank our colleagues at the Peter MacCallum Animal and Microscopy core facilities for their outstanding assistance and Prof Anthony Burgess for his highly valuable revision of the manuscript. This work was supported by a NHMRC Program Grant # 487922, NHMRC Project Grant # 1007659 and NHMRC Senior Research Fellowship # APP1002117 and a Rothschild-Yvette Mayent-Institut Curie Award Sabbatical Fellowship, Curie Institute, Paris (2009) to R.G.R. MG is supported by a Fellowship from the Swiss Science Foundation and the Novartis Foundation, Switzerland. SF was funded by the Association pour la Recherche contre le Cancer (ARC).