Targeting YAP and Hippo signaling pathway in liver cancer.
BACKGROUND
The Hippo signaling pathway plays pivotal roles in controlling both cell growth and organ size, emerging as a new paradigm in tumor suppression. Yes-associated protein (YAP) functions as a potent transcription co-activator and is a major downstream target tightly regulated by the Hippo pathway. Inactivation of the Hippo signaling induces YAP-mediated activation of various target genes that functionally causes cellular proliferation and outgrowth of organ size. Recently, YAP has been implicated as a bona fide oncogene in solid tumors, but little is known about its exact molecular mechanism in carcinogenesis.


METHODS
We discuss the latest important findings in the Hippo signaling pathway and the possible means of developing potential cancer therapeutics by targeting multiple sites along the Hippo pathway.


RESULTS
An overview of the emerging roles of YAP and Hippo signaling in oncogenesis and the possible ways of developing cancer therapies against the pathway components, downstream targets or interconnected pathways.


CONCLUSIONS
YAP is a key oncogenic driver in liver carcinogenesis and deregulation of the Hippo pathway causes tumor formation and malignancy. Targeting YAP and cognate downstream signaling targets may have clinical utility in cancer therapies.
Liu
Angela M
AM
Department of Pharmacology, National University of Singapore, 117597, Singapore.
Xu
Michelle Z
MZ
Chen
Jinfei
J
Poon
Ronnie T
RT
Luk
John M
JM
D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing; D029721:Drosophila Proteins; D017228:Hepatocyte Growth Factor; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C082332:macrophage stimulating protein; C108675:TAFAZZIN protein, human; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases