NODAL/TGFβ signalling mediates the self-sustained stemness induced by PIK3CAH1047R homozygosity in pluripotent stem cells.

ABSTRACT: Activating PIK3CA mutations are known 'drivers' of human cancer and developmental overgrowth syndromes. We recently demonstrated that the 'hotspot' PIK3CAH1047R variant exerts unexpected allele dose-dependent effects on stemness in human pluripotent stem cells (hPSCs). In this study, we combine high-depth transcriptomics, total proteomics and reverse-phase protein arrays to reveal potentially disease-related alterations in heterozygous cells, and to assess the contribution of activated TGFβ signalling to the stemness phenotype of homozygous PIK3CAH1047R cells. We demonstrate signalling rewiring as a function of oncogenic PI3K signalling strength, and provide experimental evidence that self-sustained stemness is causally related to enhanced autocrine NODAL/TGFβ signalling. A significant tra

SUBMITTER: Madsen RR 

PROVIDER: S-EPMC7969366 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature