Related Experiment Video
Updated: Feb 8, 2026
06:54
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
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Convergence for Inactivation of TGFβ Signaling Is a Common Feature of Advanced Pancreatic Cancer
Jungeui Hong1,2,3, Zachary A Kohutek4, Haochen Zhang1,5
1David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York.
Cancer Discovery
|February 6, 2026
Summary
Convergent evolution in the TGF-β pathway impacts pancreatic ductal adenocarcinoma (PDAC) metastasis. SMAD4 inactivation is linked to de novo metastasis, while TGF-β receptor inactivation is seen in locally advanced cancers.
Area of Science:
- Oncology
- Genomics
- Cancer Biology
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is a complex disease with varied metastatic potential.
- Understanding the genetic drivers of PDAC metastasis is crucial for effective treatment strategies.
Purpose of the Study:
- To investigate the genetic underpinnings of metastasis in advanced-stage PDAC.
- To identify potential biomarkers distinguishing locally advanced from metastatic PDAC.
Main Methods:
- Whole exome sequencing of 250 unique tumor tissues from 30 multi-region sampled pancreatic cancer autopsies.
- Orthotopic injection of PDAC organoids with SMAD4 versus TGFBR2 inactivation in mice for validation.
Main Results:
- Convergent evolution within the TGF-β pathway is a common feature in advanced PDAC.
- SMAD4 inactivation is more prevalent in de novo metastatic PDACs.
- TGF-β surface receptor inactivation is more common in locally advanced, non-metastatic PDACs.
- Radiated PDACs exhibited greater genomic complexity and distinct mutational signatures compared to chemotherapy-treated PDACs.
Conclusions:
- Genetic differences in TGF-β pathway inactivation correlate with metastatic propensity in PDAC.
- These findings may offer biomarkers for identifying PDAC patients who would benefit from neoadjuvant chemoradiation.
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