The Hippo pathway is an evolutionarily conserved regulator of tissue growth.
The Hippo pathway controls multiple cellular functions that are central to tumorigenesis, including proliferation and apoptosis.
Hippo pathway mutations in mice and flies give rise to tumours.
Hippo pathway activity seems to be frequently deregulated in different human cancers but most Hippo pathway genes are not commonly mutated.
Molecular events such as sensitivity to the mechanical properties of tumours and crosstalk with other cancer pathways might cause Hippo pathway deregulation in human cancers.
Hippo pathway therapeutics and new avenues to modulate pathway activity are beginning to emerge.
The Hippo pathway controls organ size in diverse species, whereas pathway deregulation can induce tumours in model organisms and occurs in a broad range of human carcinomas, including lung, colorectal, ovarian and liver cancer. Despite this, somatic or germline mutations in Hippo pathway genes are uncommon, with only the upstream pathway gene neurofibromin 2 (NF2) recognized as a bona fide tumour suppressor gene. In this Review, we appraise the evidence for the Hippo pathway as a cancer signalling network, and discuss cancer-relevant biological functions, potential mechanisms by which Hippo pathway activity is altered in cancer and emerging therapeutic strategies.
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K.F.H. is a Sylvia and Charles Viertel Senior Medical Research Fellow. X.Z. is a Cure Cancer Australia and National Breast Cancer Foundation fellow. D.M.T is an Australian National Health and Medical Research Council (NHMRC) Senior Research Fellow.
The authors declare no competing financial interests.
- 14-3-3 binding sites
Peptide sequences that bind to 14-3-3 proteins when phosphorylated. 14-3-3 proteins often function as adaptor proteins or subcellular localizers of their protein substrates.
Apoptosis resulting from inappropriate attachment of cells to a substrate.
The capability of cells to give rise to multiple lineages.
- Non-canonical WNT signalling
WNT signalling that is independent of β-catenin.
- Adherens junctions
Intercellular junctions important for epithelial cell–cell adhesion.
- Tight junctions
Intercellular junctions that form at the apical regions of epithelial cells.
- Driver mutations
Mutations that are actively involved in tumour formation.
- Passenger mutations
Mutations that are present in cancers but that do not promote tumour formation.
Distinctive for a particular disease.
- Epithelioid haemangioendothelioma
A rare vascular tumour characterized by TAZ–CAMTA1 gene fusions.
- Photocoagulation therapy
Light-based method used especially for treating retinal tears.
- Photodynamic therapy
Activation of photosensitive compounds by light.
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Harvey, K., Zhang, X. & Thomas, D. The Hippo pathway and human cancer. Nat Rev Cancer 13, 246–257 (2013). https://doi.org/10.1038/nrc3458
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