Targeting the CBP/β-Catenin Interaction to Suppress Activation of Cancer-Promoting Pancreatic Stellate Cells.

Cancers
Mingtian CheKeane K Y Lai

Abstract

Although cyclic AMP-response element binding protein-binding protein (CBP)/β-catenin signaling is known to promote proliferation and fibrosis in various organ systems, its role in the activation of pancreatic stellate cells (PSCs), the key effector cells of desmoplasia in pancreatic cancer and fibrosis in chronic pancreatitis, is largely unknown. To investigate the role of the CBP/β-catenin signaling pathway in the activation of PSCs, we have treated mouse and human PSCs with the small molecule specific CBP/β-catenin antagonist ICG-001 and examined the effects of treatment on parameters of activation. We report for the first time that CBP/β-catenin antagonism suppresses activation of PSCs as evidenced by their decreased proliferation, down-regulation of "activation" markers, e.g., α-smooth muscle actin (α-SMA/Acta2), collagen type I alpha 1 (Col1a1), Prolyl 4-hydroxylase, and Survivin, up-regulation of peroxisome proliferator activated receptor gamma (Ppar-γ) which is associated with quiescence, and reduced migration; additionally, CBP/β-catenin antagonism also suppresses PSC-induced migration of cancer cells. CBP/β-catenin antagonism represents a novel therapeutic strategy for suppressing PSC activation and may be effective at...Continue Reading

References

Oct 19, 2001·The Journal of Biological Chemistry·Atsushi MasamuneTooru Shimosegawa
Dec 12, 2003·World Journal of Gastroenterology : WJG·Atsushi MasamuneTooru Shimosegawa
Aug 18, 2004·Proceedings of the National Academy of Sciences of the United States of America·Katayoon H EmamiMichael Kahn
Jun 25, 2005·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Malte BuchholzThomas M Gress
Aug 12, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jia-Ling TeoMichael Kahn
Feb 7, 2006·European Journal of Pharmacology·Maria G BelvisiMark A Birrell
Jan 4, 2007·The Journal of Clinical Investigation·M Bishr OmaryStephen J Pandol
May 9, 2007·Gastroenterology·Samuele De MinicisRobert F Schwabe
Feb 5, 2008·Cancer Research·Rosa F HwangCraig D Logsdon
Apr 3, 2008·Cancer Research·Alain VonlaufenMinoti V Apte
Jul 28, 2010·Proceedings of the National Academy of Sciences of the United States of America·William R HendersonMichael Kahn
Aug 3, 2010·The Journal of Biological Chemistry·Ying CaoDebabrata Mukhopadhyay
Nov 18, 2010·Biochemical and Biophysical Research Communications·Kazuhiro KikutaTooru Shimosegawa
Aug 6, 2011·Journal of the American Society of Nephrology : JASN·Sha HaoYouhua Liu
Jun 12, 2012·Cell·Hans Clevers, Roel Nusse
Sep 14, 2012·Frontiers in Physiology·Minoti V ApteJeremy S Wilson
Apr 19, 2013·Annals of the Rheumatic Diseases·Christian BeyerJörg H W Distler
Apr 30, 2013·Gastroenterology·Minoti V ApteStephen J Pandol
Feb 20, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Clifford J WhatcottHaiyong Han
Mar 10, 2015·Gastroenterology·Satdarshan Pal Monga
Aug 10, 2015·Gastroenterology·David C WhitcombRandall E Brand
May 16, 2017·Digestive Diseases and Sciences·Daniel LewStephen Pandol
Aug 2, 2017·The American Journal of Gastroenterology·Jakob KirkegårdDeirdre Cronin-Fenton
Dec 9, 2017·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Büsra Öztürk AkcoraRuchi Bansal
Jul 4, 2018·Frontiers in Physiology·Ran XueJianyu Hao
Mar 7, 2019·Current Molecular Pharmacology·Keane K Y LaiMichael Kahn
Jan 14, 2020·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Srinivasa P PothulaMinoti V Apte

❮ Previous
Next ❯

Citations

Aug 13, 2020·International Journal of Molecular Sciences·Cristiana TanaseMihail Eugen Hinescu
Dec 6, 2020·Journal of Hematology & Oncology·Ya Zhang, Xin Wang
Mar 11, 2021·Drug Design, Development and Therapy·Xiaoyuan WangRenping Huang
May 1, 2021·International Journal of Molecular Sciences·Silvia MuccioliRoberto Costa
Jun 18, 2021·Advanced Drug Delivery Reviews·Alexandros Marios SofiasTwan Lammers

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR

Software Mentioned

ImageLab
ImageJ

Related Concepts

Related Feeds

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.