Oncogenic PIK3CA corrupts growth factor signaling specificity

ABSTRACT: Technical limitations have prevented understanding of how growth factor signals are encoded in distinct activity patterns of the phosphoinositide 3-kinase (PI3K)/AKT pathway, and how this is altered by oncogenic pathway mutations. We introduce a kinetic, single-cell framework for precise calculations of PI3K-specific information transfer for different growth factors. This features live-cell imaging of PI3K/AKT activity reporters and multiplexed CyTOF measurements of PI3K/AKT and RAS/ERK signaling markers over time. Using this framework, we found that the PIK3CAH1047R oncogene was not a simple, constitutive activator of the pathway as often presented. Dose-dependent expression of PIK3CAH1047R in human cervical cancer and induced pluripotent stem cells corrupted the fidelity of growth factor

SUBMITTER: Dr Ralitsa, Radostinova Radostinova Madsen 

PROVIDER: S-SCDT-10_1038-S44320-024-00078-X | biostudies-other |

REPOSITORIES: biostudies-other