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Targeting the CBP/β-Catenin Interaction to Suppress Activation of Cancer-Promoting Pancreatic Stellate Cells
- 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.
- Subjects :
- 0301 basic medicine
Cancer Research
pancreatic cancer
pancreatitis
p300
pancreatic stellate cells
CBP
lcsh:RC254-282
03 medical and health sciences
0302 clinical medicine
Pancreatic cancer
Survivin
medicine
Chemistry
Communication
fibrosis
Wnt signaling pathway
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Wnt signaling
Collagen, type I, alpha 1
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Catenin
Cancer cell
Hepatic stellate cell
Cancer research
Signal transduction
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 12
- Issue :
- 1476
- Database :
- OpenAIRE
- Journal :
- Cancers
- Accession number :
- edsair.doi.dedup.....1df0e4fdbc44415831c2d9a6d7d9d26b