Back to Search Start Over

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

Authors :
Keane K Y Lai
Aurelia Lugea
Jia-Ling Teo
Mingtian Che
Laleh G. Melstrom
Yate-Ching Yuan
Soo-Mi Kweon
Stephen J. Pandol
Richard T. Waldron
Raul Urrutia
Source :
Cancers, Vol 12, Iss 1476, p 1476 (2020), Cancers
Publication Year :
2020
Publisher :
MDPI AG, 2020.

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: CBP/β-catenin antagonism represents a novel therapeutic strategy for suppressing PSC activation and may be effective at countering PSC promotion of pancreatic cancer.

Details

Language :
English
ISSN :
20726694
Volume :
12
Issue :
1476
Database :
OpenAIRE
Journal :
Cancers
Accession number :
edsair.doi.dedup.....1df0e4fdbc44415831c2d9a6d7d9d26b