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Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Hippo pathway is the major regulator of organ growth and proliferation. Described initially in Drosophila, it is now recognized as one of the most conserved molecular pathways in all metazoan. Recent studies have revealed the Hippo signalling pathway might contribute to tumorigenesis and cancer development. The core components of the Hippo pathway include the mammalian sterile 20-like kinases (MSTs), large tumour suppressor kinases (LATSs), the adaptor proteins Salvador homologue 1 (SAV1, also called WW45) and Mps One Binder kinase activator proteins. The major target of the Hippo core kinases is the mammalian transcriptional activator Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ). In cancer, the Hippo signalling is inactivated and YAP and TAZ are activated and free to translocate into the nucleus to promote cell proliferation. Nuclear YAP/TAZ activate or suppress transcription factors that regulate target genes involved in cell proliferation, tissue growth, control of organ size and shape or metastasis. The Hippo signalling pathway that controls the most important cellular processes like growth and division appears to be a very promising research subject in the field of cell biology and tissue engineering. It consists of elements that in the cell play the roles of tumour suppressors as well as oncogenes. This 'Janus like' - an opposite activity hidden within one and the same signalling pathway represents a significant obstacle for studying it. This property of the Hippo pathway is worth remembering, as it will appear several times during the discussion of its properties. Here, we will review certain data regarding biology of the Hippo signalling and its interplay with other prominent signalling pathways in the cell, its relevance in cancer development and therapies that might target elements of the Hippo pathway in most human cancers.
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PMID:Hippo pathway - brief overview of its relevance in cancer. 2882 Mar 89

Niches have traditionally been characterised as signalling microenvironments that allow stem cells to maintain their fate. This definition implicitly assumes that the various niche signals are integrated towards a binary fate decision between stemness and differentiation. However, observations in multiple systems have demonstrated that stem cell properties, such as proliferation and self-renewal, can be uncoupled at the level of niche signalling input, which is incompatible with this simplified view. We have studied the role of the transcriptional regulator Zfh1, a shared target of the Hedgehog and Jak/Stat niche signalling pathways, in the somatic stem cells of the Drosophila testis. We found that Zfh1 binds and downregulates salvador and kibra, two tumour suppressor genes of the Hippo/Wts/Yki pathway, thereby restricting Yki activation and proliferation to the Zfh1+ stem cells. These observations provide an unbroken link from niche signal input to an individual aspect of stem cell behaviour that does not, at any step, involve a fate decision. We discuss the relevance of these findings for an overall concept of stemness and niche function.
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PMID:Direct control of somatic stem cell proliferation factors by the Drosophila testis stem cell niche. 3000 31

Osteosarcoma (OS) is a primary malignant bone tumour which usually occurs in children and adolescents. OS is primarily a result of chromosomal aberrations, a combination of acquired genetic changes and, hereditary, resulting in the dysregulation of cellular functions. The Hippo signalling pathway regulates cell and tissue growth by modulating cell proliferation, differentiation, and migration in developing organs. Mammalian STE20-like 1/2 (MST1/2) protein kinases are activated by neurofibromatosis type 2, Ras association domain family member 2, kidney and brain protein, or other factors. Interactions between MST1/2 and salvador family WW domain-containing protein 1 activate large tumour suppressor kinase 1/2 proteins, which in turn phosphorylate the downstream Yes-associated protein 1/transcriptional coactivator with PDZ-binding motif (YAP/TAZ). Moreover, dysregulation of this pathway can lead to aberrant cell growth, resulting in tumorigenesis. Interestingly, small molecules targeting the Hippo signalling pathways, through affecting YAP/TAZ cellular localisation and their interaction with members of the TEA/ATTS domain family of transcriptional enhancers are being developed and hold promise for the treatment of OS. This review discusses the existing knowledge about the involvement of the Hippo signalling cascade in OS and highlights several small molecule inhibitors as potential novel therapeutics.
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PMID:The Hippo in the room: Targeting the Hippo signalling pathway for osteosarcoma therapies. 3269 58