Transforming growth factor-beta responsiveness in DPC4/SMAD4-null cancer cells

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Updated: Oct 19, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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

J L Dai1, M Schutte, R K Bansal

  • 1Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.

Molecular Carcinogenesis
|September 16, 1999
PubMed

Insights

DPC4/SMAD4 alterations are frequent in pancreatic cancer. TGFbeta responses can be DPC4-independent, relying on the ras pathway, suggesting a new categorization of TGFbeta signaling.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • DPC4/SMAD4 is a candidate tumor suppressor gene frequently altered in pancreatic cancer.
  • Its tumor-suppressive function is linked to the transforming growth factor-beta (TGFbeta) pathway.

Purpose of the Study:

  • To investigate the role of DPC4 in TGFbeta signaling in pancreatic cancer.
  • To determine if TGFbeta responses are DPC4-dependent or independent in pancreatic cancer cells.

Main Methods:

  • Utilized DPC4-null pancreatic cancer cell lines with natural homozygous deletion.
  • Engineered clones for stable expression of wild-type DPC4.
  • Compared TGFbeta responses in DPC4-null and DPC4-expressing cells.
  • Analyzed TGFbeta responses in parallel using a breast cancer cell line.

Main Results:

  • TGFbeta growth-inhibitory and transcriptional responses were DPC4-independent in DPC4-null pancreatic cancer cells.
  • This independence was maintained even after reintroducing DPC4.
  • In contrast, TGFbeta responses were DPC4-dependent in a parallel breast cancer cell line.
  • TGFbeta-induced growth inhibition in DPC4-null cells depended on an intact ras effector pathway.

Conclusions:

  • TGFbeta responses can be categorized into DPC4-dependent and DPC4-independent signaling pathways.
  • Disruption of the TGFbeta-independent pathway may drive DPC4 alterations during pancreatic tumorigenesis.

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