Highlights d Lung cancer progression is accompanied by a stereotypic expansion of heterogeneity d Cell state heterogeneity arises largely independently of genetic variation d State transitions occur via an HPCS harboring high differentiation and growth capacity d The HPCS is drug resistant and portends poor patient survival across all cancers

Significance Nuclear envelope breakdown (NEB) leads to the exposure of nuclear structures to cytoplasmic activities. Greatwall is a kinase able to inhibit PP2A phosphatases that counteract Cdk-dependent phosphorylation required for mitosis. Here we show that Greatwall, an essential protein in mammals, is exported to the cytoplasm in a Cdk-dependent manner before NEB, thus protecting mitotic phosphates from phosphatase activity.

Cip1 .

No abstract