The Hippo/MST2 (mammalian sterile 20-like kinase 2) pathway is a signalling cascade evolutionarily conserved in its structure. Originally described in Drosophila melanogaster as a regulator of organ size, this pathway has greater functions in mammals. Disturbance of mammalian MST2 pathway is associated with tumorigenesis by affecting apoptosis, cell cycle and polarity. In addition, this pathway has been shown to cross-talk with mitogenic pathways at multiple levels. In the present mini-review, we discuss our contribution highlighting the regulation of MST2 signalling by frequently observed oncogenic perturbations affecting mitogenic pathways. In particular, we review the role of RAS isoforms and PI3K (phosphoinositide 3-kinase)/Akt in the regulation of MST2 activity by phosphorylation. We also put the emphasis on RAF-induced control of MST2 signalling by protein–protein interactions. Finally, we recapitulate some of the direct mechanisms, such as ubiquitin-dependent degradation or gene silencing by promoter hypermethylation, involved in MST2 pathway component down-regulation in cancers.
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August 2014
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Conference Article|
August 11 2014
One Hippo and many masters: differential regulation of the Hippo pathway in cancer
David Romano;
David Romano
1
*Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland
1Correspondence may be addressed to either of these authors (emaildavid.romano@ucd.ie or walter.kolch@ucd.ie).
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David Matallanas;
David Matallanas
*Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland
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Dennie T. Frederick;
Dennie T. Frederick
†Division of Surgical Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, U.S.A.
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Keith T. Flaherty;
Keith T. Flaherty
‡Division of Medical Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, U.S.A.
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Walter Kolch
Walter Kolch
1
*Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland
§Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
∥School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland
1Correspondence may be addressed to either of these authors (emaildavid.romano@ucd.ie or walter.kolch@ucd.ie).
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Publisher: Portland Press Ltd
Received:
January 21 2014
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem Soc Trans (2014) 42 (4): 816–821.
Article history
Received:
January 21 2014
Citation
David Romano, David Matallanas, Dennie T. Frederick, Keith T. Flaherty, Walter Kolch; One Hippo and many masters: differential regulation of the Hippo pathway in cancer. Biochem Soc Trans 1 August 2014; 42 (4): 816–821. doi: https://doi.org/10.1042/BST20140030
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