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.
Current Drug Targets
Title:The Hippo Pathway as Drug Targets in Cancer Therapy and Regenerative Medicine
Volume: 18 Issue: 4
Author(s): Shunta Nagashima, Yijun Bao and Yutaka Hata
Affiliation:
Keywords: Cancer, drug screening, regeneration, sarcopenia, tumor suppressor.
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.
Export Options
About this article
Cite this article as:
Nagashima Shunta, Bao Yijun and Hata Yutaka, The Hippo Pathway as Drug Targets in Cancer Therapy and Regenerative Medicine, Current Drug Targets 2017; 18 (4) . https://dx.doi.org/10.2174/1389450117666160112115641
DOI https://dx.doi.org/10.2174/1389450117666160112115641 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
Drug-Targeted Approach with Polymer Nanocomposites for Improved Therapeutics
Polymer nanocomposites have been recognized as an advanced and cutting-edge technique in drug targeting administration. These materials combine the unique features of nanoparticles with the adaptability of polymers to produce highly personalized drug administration devices. Integrating nanoparticles containing pharmaceuticals into a polymer matrix enables researchers to regulate the rates at ...read more
RNA Molecules in the Treatment of Human Diseases
Messenger and non-coding RNAs, including long and small transcripts, are mediators of gene expression. Gene expression at the RNA level shows significant aberrations in human diseases, including cancer, leukemia, lymphoma, cardiovascular diseases, and neurological disorders. Human transcripts serve either as biomarkers of diagnosis, prognosis, prediction of treatment response and/or therapy ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Targeting the SUMO E2 Conjugating Enzyme Ubc9 Interaction for Anti-Cancer Drug Design
Anti-Cancer Agents in Medicinal Chemistry Editorial [Hot topic: In Vitro Imaging (Guest Editors: Flora Tang and Jinghai J. Xu)]
Combinatorial Chemistry & High Throughput Screening Current Molecularly Targeting Therapies in NSCLC and Melanoma
Anti-Cancer Agents in Medicinal Chemistry Harnessing Polypharmacology with Computer-Aided Drug Design and Systems Biology
Current Pharmaceutical Design Future Prospects for Old Chemotherapeutic Drugs in the Target-Specific Era; Pharmaceutics, Combinations, Co-Drugs and Prodrugs with Melphalan as an Example
Letters in Drug Design & Discovery Chalcones Derivatives Acting as Cell Cycle Blockers: Potential Anti Cancer Drugs?
Current Drug Targets Novel Targets in Multiple Sclerosis: To Oxidative Stress and Beyond
Current Topics in Medicinal Chemistry NAD Metabolism and Functions: A Common Therapeutic Target for Neoplastic, Metabolic and Neurodegenerative Diseases
Current Topics in Medicinal Chemistry The Advance of Dendrimers - A Versatile Targeting Platform for Gene/Drug Delivery
Current Pharmaceutical Design Increased Expression of Matrix Metalloproteinases Mediates Thromboxane A2-Induced Invasion in Lung Cancer Cells
Current Cancer Drug Targets Immunophilin Dysfunction and Neuropathology
Current Medicinal Chemistry Palladium-Catalyzed Oxyarylation, Azaarylation and α-Arylation Reactions in the Synthesis of Bioactive Isoflavonoid Analogues
Current Organic Synthesis Natural Compounds in the Chemoprevention of Malignant Melanoma
Anti-Cancer Agents in Medicinal Chemistry Progress in Chemo- and Regioselective Transformations of Symmetrical Cephalostatin Analogues
Letters in Organic Chemistry The TGF-β Signaling Pathway as a Pharmacological Target in a Hepatocellular Carcinoma
Current Pharmaceutical Design The Management of Thymoma - A Review of the Status Quo with Practical Treatment Recommendations
Current Respiratory Medicine Reviews Folic Acid Conjugated Chitosan Nanoparticles for Tumor Targeting of Therapeutic and Imaging Agents
Pharmaceutical Nanotechnology Fluorescence Detection of MMP-9. I. MMP-9 Selectively Cleaves Lys-Gly-Pro-Arg-Ser-Leu-Ser-Gly-Lys Peptide
Current Pharmaceutical Biotechnology Fertility Preservation for Young Women with Cancer: Hope for the Future
Current Women`s Health Reviews Organic Fluorescent Dye-based Nanomaterials: Advances in the Rational Design for Imaging and Sensing Applications
Current Medicinal Chemistry