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Remaining drug-tolerant persistent (DTP) cancer cells limit the efficacy of targeted therapy in EGFR, ALK and KRAS mutant non-small cell lung cancer (NSCLC). Here, the authors show that focal adhesion kinase (FAK)-YAP signalling supports DTP cells promoting residual disease and targeting this pathway improved tumour response in NSCLC preclinical models.

Aligned collagen I is associated with the emergence of leader cells that are responsible for collective invasion. Here, the authors show that Collagen I and Yap signalling are in a feed-forward loop to drive the collective invasion of basal-like tumour cells.

The precise mechanisms of neuronal cell death in neurodegeneration are not fully understood. Here the authors show that YAP-mediated neuronal necrosis is increased in pre-symptomatic stages of Alzheimer’s disease and intervention to the necrosis rescues extracellular Aβ aggregation and symptoms in a mouse model.

Hippo and Wnt pathways are important for cancer development, and they can cross talk; however, the mechanisms behind this connection are unknown. Here the authors show that DVL (a scaffold protein in the Wnt pathway) regulates the shuttling of YAP (a key component of the Hippo pathway) between cytoplasm and nucleus in specific tumor suppressor contexts.

It is unclear how specific signalling pathways are coordinated to generate pathologically activated cancer associated fibroblasts (CAFs). Here, Ferrari et al show that stromal expression of Dickkopf-3 (DKK3) associates with aggressive tumours. DKK3 is a HSF-1 effector that activates β-catenin and YAP/TAZ, and DKK3-driven YAP/TAZ activation regulates the pro-tumorigenic behaviour of CAFs.

Zhang et al. show that YAP and TAZ suppress nucleic acid sensing and antiviral responses by inhibiting the TBK1 kinase. Conversely, Hippo pathway activity inactivates YAP/TAZ to relieve TBK1 suppression and enhance antiviral defence in zebrafish.

Li et al. define an adaptive resistance mechanism against FGFR inhibitor treatment in breast cancer attributed to loss of BRG1 chromatin recruitment, reactivation of YAP-dependent enhancers and upregulation of amino acid-induced mTORC1 activity.

Li et al. show that ROR1–HER3 receptor tyrosine kinase signalling in breast cancer cells inhibits the MST1/2 Hippo pathway kinases through a lncRNA termed MAYA. The resulting activation of YAP promotes osteoclast differentiation for bone metastasis.

The marine compound microcolin B stimulates the Hippo pathway and selectively kills YAP-dependent cancer cells by inhibiting phosphatidylinositol transfer protein and depleting plasma membrane phosphatidylinositol-4-phosphate.

Liu et al. show that statin enhances cardiovascular disease protection through epigenetic modulation of YAP–SOX9 signaling, improving endothelial function and offering new therapeutic strategies.

Hippo pathway inactivation plays a role in many cancers, although how tumor cells depress signaling is unclear. Here, Lim et al. identify STK25, which activates LATS in a manner distinct from other upstream kinases and is focally deleted from a range of human cancers.

A variety of signals have been reported to either activate or inhibit the Hippo kinase cascade. Here, Meng et al. show that mitogen activated protein kinase kinase kinase kinase (MAP4K) family members function in parallel to and are partially redundant with MST1/2 in regulating LATS in response to upstream signals.

Here, the authors identify the host proteins LATS1/2 and YAP of the Hippo pathway to regulate Ebola virus transcription and virus production/egress. They show that YAP activity is important for virus particle production and release, while LATS1/2 are critical for EBOV mRNA synthesis and viral protein expression.

Using visible-light-induced crosslinking, a local stiffening approach is developed for ex vivo mouse and human lung tissue as an early lung injury model, directing epithelial cell mechanosensing, differentiation and nascent protein deposition.

Inhibition of a cardiac stroma-enriched mechanosensor, SRC—in concert with suppression of the TGFβ pathway—potentiates the reversal of fibroblast activation and alleviates contractile dysfunction in fibrotic hearts.

Laminin, an important component of the extracellular matrix supporting the epithelium, hinders the typical mechanoresponse of epithelial cells to an increase in substrate stiffness, by protecting the cell nucleus from mechanical deformation.

Han et al. report that the Hippo pathway kinases LATS1 and LATS2 phosphorylate the heavy metal response transcription factor MTF1, leading to attenuation of heavy metal response gene transcription and cellular detoxification.

Mechanical cues from the local cellular microenvironment can direct cell fate. Now, experiments with human mesenchymal stem cells cultured on phototunable soft poly(ethylene glycol) hydrogels show that the cells remember past physical environments—with the transcriptional co-activators YAP and TAZ acting as a mechanical rheostat—and therefore that appropriate doses of mechanical cues can be used to manipulate the cells’ fate.

Structural changes mediated by advanced glycation end-products enhance extracellular matrix viscoelasticity, and that viscoelasticity can promote cancer progression in vivo, independent of stiffness.

The Ras-related GTPase RAP2 is a key intracellular signal transducer by which extracellular matrix rigidity controls mechanosensitive cellular activities through YAP and TAZ.

Non alcoholic fatty liver disease (NAFLD) associates with an elevated risk of developing hepatocellular carcinoma (HCC). Here, the authors find that Nogo-B, an endoplasmic reticulum resident protein, is upregulated by lipid uptake and acts as an oncogene in NAFLD-associated HCC by promoting lipid droplet breakdown by lipophagy and triggering Hippo pathway dysregulation

Lin et al. find that stress-induced p38 MAPK activation leads to cytoplasmic relocation of the Hippo pathway nuclear transcription factor TEAD. TEAD relocation causes inhibition of YAP activity and suppresses YAP-driven cancer cell growth.

Morphogenesis of tissue sheets is well studied, but mechanisms that shape bulk tissues are unclear. Here, the authors show that mesenchymal cells intercalate in 3D to shape the mouse branchial arch, with cortical forces driving intercalations in a Wnt5a-, Yap/Taz- and Piezo1-dependent manner.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Intestinal stem cells are responsible for replenishing cells within the high-turnover intestinal epithelium. Here they show that ribosome dynamics affect intestinal stem cell identity through a mechanism that is triggered by changes in nutrient availability.

Glycogen Synthase Kinase 3 (GSK3) has conserved functions across species but its role in the kidney is unclear. Here, the authors show that in the kidney podocyte cell of mice and related nephrocyte in Drosophila that GSK3 is a master regulator of function both during development and in maturity.

Human mesenchymal stem cells can be mechanically and pharmacologically conditioned to enhance vascular regeneration in vivo, as shown in mice with hindlimb ischaemia.

The microvasculature is critical for delivery of oxygen and metabolites throughout tissues. Here they use human blood vessel organoids to show that CTGF is a critical paracrine regulator of microvascular integrity that can restore pericyte coverage and vessel structure.