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Updated: May 8, 2026
Oncogene Expression Analysis with Alterations in pH in a Pancreatic Ductal Cell Line
Published on: April 11, 2025
Reduced expression of bone morphogenetic protein receptor IA in pancreatic cancer is associated with a poor prognosis
P W Voorneveld1, V Stache, R J Jacobs
1Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
Background:
The expression of SMAD4, the central component of the transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signalling pathways, is lost in 50% of pancreatic cancers and is associated with a poor survival. Although the TGF-β pathway has been extensively studied and characterised in pancreatic cancer, there is very limited data on BMP signalling, a well-known tumour-suppressor pathway. BMP signalling can be lost not only at the level of SMAD4 but also at the level of BMP receptors (BMPRs), as has been described in colorectal cancer.
Methods:
We performed immunohistochemical analysis of the expression levels of BMP signalling components in pancreatic cancer and correlated these with survival. We also manipulated the activity of BMP signalling in vitro.
Results:
Reduced expression of BMPRIA is associated with a significantly worse survival, primarily in a subset of SMAD4-positive cancers. In vitro inactivation of SMAD4-dependent BMP signalling increases proliferation and invasion of pancreatic cancer cells, whereas inactivation of BMP signalling in SMAD4-negative cells does not change the proliferation and invasion or leads to an opposite effect.
Conclusion:
Our data suggest that BMPRIA expression is a good prognostic marker and that the BMP pathway is a potential target for future therapeutic interventions in pancreatic cancer.
Insights
Reduced BMPRIA expression indicates poor survival in pancreatic cancer patients. BMP signaling is a potential therapeutic target for this disease.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Signaling Pathways
Background:
- SMAD4 loss occurs in 50% of pancreatic cancers, impacting TGF-β and BMP signaling.
- BMP signaling, a known tumor suppressor, is understudied in pancreatic cancer.
- BMP signaling loss can involve BMP receptors, similar to colorectal cancer findings.
Purpose of the Study:
- Investigate the role of BMP signaling components in pancreatic cancer.
- Determine the prognostic value of BMP signaling in pancreatic cancer survival.
- Explore BMP signaling as a therapeutic target in pancreatic cancer.
Main Methods:
- Immunohistochemical analysis of BMP signaling components in pancreatic tumors.
- Correlation of BMP signaling component expression with patient survival.
- In vitro manipulation of BMP signaling activity in pancreatic cancer cells.
Main Results:
- Reduced BMPRIA expression significantly correlates with worse survival, particularly in SMAD4-positive cancers.
- Inactivation of SMAD4-dependent BMP signaling enhances pancreatic cancer cell proliferation and invasion.
- BMP signaling inactivation in SMAD4-negative cells shows no effect or an opposite effect on proliferation and invasion.
Conclusions:
- BMPRIA expression serves as a valuable prognostic marker in pancreatic cancer.
- The BMP signaling pathway represents a promising therapeutic target for pancreatic cancer treatment.
