The Hippo Pathway as a Driver of Select Human Cancers

Aishwarya Kulkarni; Matthew T Chang; Joseph H A Vissers; Anwesha Dey; Kieran F Harvey

doi:10.1016/j.trecan.2020.04.004

The Hippo Pathway as a Driver of Select Human Cancers

Trends Cancer. 2020 Sep;6(9):781-796. doi: 10.1016/j.trecan.2020.04.004. Epub 2020 May 20.

Authors

Aishwarya Kulkarni¹, Matthew T Chang², Joseph H A Vissers³, Anwesha Dey², Kieran F Harvey⁴

Affiliations

¹ Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia.
² Departments of Discovery Oncology and Bioinformatics, Genentech Inc., South San Francisco, CA 94080, USA.
³ Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia; Centre for Cancer Research and Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia.
⁴ Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia; Department of Anatomy and Developmental Biology, and Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia. Electronic address: kieran.harvey@petermac.org.

PMID: 32446746
DOI: 10.1016/j.trecan.2020.04.004

Abstract

The Hippo pathway regulates myriad biological processes in diverse species and is a key cancer signaling network in humans. Although Hippo has been linked to multiple aspects of cancer, its role in this disease is incompletely understood. Large-scale pan-cancer analyses of core Hippo pathway genes reveal that the pathway is mutated at a high frequency only in select human cancers, including malignant mesothelioma and meningioma. Hippo pathway deregulation is also enriched in squamous epithelial cancers. We discuss cancer-related functions of the Hippo pathway and potential explanations for the cancer-restricted mutation profile of core Hippo pathway genes. Greater understanding of Hippo pathway deregulation in cancers will be essential to guide the imminent use of Hippo-targeted therapies.

Keywords: Hippo pathway; meningioma; mesothelioma; pan-cancer analysis.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Antineoplastic Agents / pharmacology*
Antineoplastic Agents / therapeutic use
Biomarkers, Tumor / antagonists & inhibitors
Biomarkers, Tumor / genetics*
Biomarkers, Tumor / metabolism
Carcinogenesis / genetics
Carcinogenesis / pathology
Cell Competition / genetics
Cell Differentiation / genetics
Cell Proliferation / genetics
Drug Resistance, Neoplasm / drug effects
Drug Resistance, Neoplasm / genetics
Hippo Signaling Pathway
Humans
Molecular Targeted Therapy / methods
Mutation
Neoplasms / drug therapy
Neoplasms / genetics*
Neoplasms / pathology
Precision Medicine / methods
Protein Serine-Threonine Kinases / antagonists & inhibitors
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*
Signal Transduction / drug effects
Signal Transduction / genetics*
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / antagonists & inhibitors
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / genetics
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / metabolism
Tumor Suppressor Proteins / antagonists & inhibitors
Tumor Suppressor Proteins / genetics
Tumor Suppressor Proteins / metabolism
Ubiquitin Thiolesterase / antagonists & inhibitors
Ubiquitin Thiolesterase / genetics
Ubiquitin Thiolesterase / metabolism

Substances

Antineoplastic Agents
BAP1 protein, human
Biomarkers, Tumor
TRAF7 protein, human
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Tumor Suppressor Proteins
Protein Serine-Threonine Kinases
Ubiquitin Thiolesterase