The Salvador/Warts/Hippo (Hippo) signaling pathway defines a novel signaling cascade regulating cell contact inhibition, organ size control, cell growth, proliferation, apoptosis and cancer development in mammals. The upstream regulation of this pathway has been less well defined than the core kinase cassette. KIBRA has been shown to function as an upstream member of the Hippo pathway by influencing the phosphorylation of LATS and YAP, but functional consequences of these biochemical changes have not been previously addressed. We show that in MCF10A cells, loss of KIBRA expression displays epithelial-to-mesenchymal transition (EMT) features, which are concomitant with decreased LATS and YAP phosphorylation, but not MST1/2. In addition, ectopic KIBRA expression antagonizes YAP via the serine 127 phosphorylation site and we show that KIBRA, Willin and Merlin differentially regulate genes controlled by YAP. Finally, reduced KIBRA expression in primary breast cancer specimens correlates with the recently described claudin-low subtype, an aggressive sub-group with EMT features and a poor prognosis.

Highlights d SARS-CoV-2 infection in induced lung cells is characterized by phosphoproteomics d Analysis of response reveals host cell signaling and protein expression profile d Comparison to studies in undifferentiated cell lines shows unique pathology in iAT2s d Systems-level predictions find druggable pathways that can impede viral life cycle

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Patient-specific iPSCs carrying an SFTPC mutation reveal the intrinsic alveolar epithelial dysfunction at the inception of interstitial lung disease Graphical abstract Highlights d Patient-specific iAEC2s serve as a human preclinical platform for modeling ILD d Patient-derived iAEC2s expressing mutant SFTPC I73T have diminished progenitor capacity d SFTPC I73T mutant iAEC2s display proteostasis perturbations and metabolic reprogramming d Mutant iAEC2s are an important proinflammatory hub via activation of the NF-kB pathway

Our understanding of the FERM (4.1/ezrin/radixin/moesin) protein family has been rapidly expanding in the last few years, with the result that many new physiological functions have been ascribed to these biochemically unique proteins. In the present review, we will discuss a number of new FRMD (FERM domain)-containing proteins that were initially discovered from genome sequencing but are now being established through biochemical and genetic studies to be involved both in normal cellular processes, but are also associated with a variety of human diseases.