Journal ArticleDOI
Hippo signaling pathway in liver and pancreas: the potential drug target for tumor therapy.
TLDR
Several small molecules currently available that can target Hippo-YAP pathway for potential treatment of hepatic and pancreatic cancers are summarized, providing clues for other YAP initiated cancers therapy as well.Abstract:
Cell behaviors, including proliferation, differentiation and apoptosis, are intricately controlled during organ development and tissue regeneration. In the past 9 years, the Hippo signaling pathway has been delineated to play critical roles in organ size control, tissue regeneration and tumorigenesis through regulating cell behaviors. In mammals, the core modules of the Hippo signaling pathway include the MST1/2-LATS1/2 kinase cascade and the transcriptional co-activators YAP/TAZ. The activity of YAP/TAZ is suppressed by cytoplasmic retention due to phosphorylation in the canonical MST1/2-LATS1/2 kinase cascade-dependent manner or the non-canonical MST1/2- and/or LATS1/2-independent manner. Hippo signaling pathway, which can be activated or inactivated by cell polarity, contact inhibition, mechanical stretch and extracellular factors, has been demonstrated to be involved in development and tumorigenesis of liver and pancreas. In addition, we have summarized several small molecules currently available that can target Hippo-YAP pathway for potential treatment of hepatic and pancreatic cancers, providing clues for other YAP initiated cancers therapy as well.read more
Citations
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Targeting Multiple Effector Pathways in Pancreatic Ductal Adenocarcinoma with a G-Quadruplex-Binding Small Molecule
Chiara Marchetti,Katherine G. Zyner,Stephan A. Ohnmacht,Mathew Robson,Shozeb Haider,Jennifer P. Morton,Giovanni Marsico,Tam Vo,Sarah Laughlin-Toth,Ahmed A. Ahmed,Gloria Di Vita,Ingrida Pazitna,Mekala Gunaratnam,Rachael J. Besser,Ana C. G. Andrade,Seckou Diocou,Jeremy A. Pike,David Tannahill,R. Barbara Pedley,T.R. Jeffry Evans,W. David Wilson,Shankar Balasubramanian,Stephen Neidle +22 more
TL;DR: The changes produced by CM03 represent a global response to the complexity of human PDAC and may be applicable to other currently hard-to-treat cancers.
Journal ArticleDOI
Upregulation of miR-181c contributes to chemoresistance in pancreatic cancer by inactivating the Hippo signaling pathway
TL;DR: Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and enhanced expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo.
Journal ArticleDOI
Neratinib inhibits Hippo/YAP signaling, reduces mutant K-RAS expression, and kills pancreatic and blood cancer cells
Paul Dent,Laurence Booth,Jane L. Roberts,Junchen Liu,Andrew Poklepovic,Alshad S. Lalani,David A. Tuveson,Jennifer Martinez,John F. Hancock +8 more
TL;DR: The data demonstrate that neratinib coordinately suppresses both mutant K-RAS and YAP function to kill pancreatic tumor cells and was enhanced by knock down of YAP.
Journal ArticleDOI
Molecular Features of the YAP Inhibitor Verteporfin: Synthesis of Hexasubstituted Dipyrrins as Potential Inhibitors of YAP/TAZ, the Downstream Effectors of the Hippo Pathway
Floriane Gibault,Fabrice Bailly,Matthieu Corvaisier,Mathilde Coevoet,Guillemette Huet,Patricia Melnyk,Philippe Cotelle +6 more
TL;DR: The data suggest that, due to their chemical structures, porphyrin‐ and dipyrrin‐related derivatives can directly target YAP and/or TAZ proteins and inhibit TEAD transcriptional activity.
Journal ArticleDOI
Modular and Adaptable Tumor Niche Prepared from Visible Light Initiated Thiol-Norbornene Photopolymerization
TL;DR: A co-initiator/comonomer-free visible light initiated thiol-norbornene photopolymerization scheme to prepare modular biomimetic hydrogels suitable for in situ cell encapsulation and the effects of cell density and gel modulus on the formation of pancreatic ductal adenocarcinoma (PDAC) spheroids is reported.
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Journal ArticleDOI
The Hippo Signaling Pathway Coordinately Regulates Cell Proliferation and Apoptosis by Inactivating Yorkie, the Drosophila Homolog of YAP
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