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The Hippo Pathway as Drug Targets in Cancer Therapy and Regenerative Medicine

[ Vol. 18 , Issue. 4 ]

Author(s):

Shunta Nagashima, Yijun Bao and Yutaka Hata   Pages 447 - 454 ( 8 )

Abstract:


Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ) co-operate with numerous transcription factors to regulate gene transcriptions. YAP1 and TAZ are negatively regulated by the tumor suppressive Hippo pathway. In human cancers, the Hippo pathway is frequently deregulated and YAP1 and TAZ escape the inhibition by the Hippo pathway. The upregulation of YAP1 and TAZ induces epithelial-mesenchymal transition and increases drug resistance in cancer cells. TAZ is implicated in cancer stemness. In consequence cancers with hyperactive YAP1 and TAZ are associated with poor clinical prognosis. Inhibitors of YAP1 and TAZ are reasoned to be beneficial in cancer therapy. On the other hand, since YAP1 and TAZ play important roles in the regulation of various tissue stem cells and in tissue repair, activators of YAP1 and TAZ are useful in the regenerative medicine. We discuss the potential application of inhibitors and activators of YAP1 and TAZ in human diseases and review the progress of drug screenings to search for them.

Keywords:

Cancer, drug screening, regeneration, sarcopenia, tumor suppressor.

Affiliation:

Department of Medical Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519

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