The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
TGF-β Tumor Suppression through a Lethal EMT
Open accessAbstract
TGF-β signaling can be pro-tumorigenic or tumor suppressive. We investigated this duality in pancreatic ductal adenocarcinoma (PDA), which, with other gastrointestinal cancers, exhibits frequent inactivation of the TGF-β mediator Smad4. We show that TGF-β induces an epithelial-mesenchymal transition (EMT), generally considered a pro-tumorigenic event. However, in TGF-β sensitive PDA cells, EMT becomes lethal by converting TGF-β-induced Sox4 from an enforcer of tumorigenesis into a promoter of apoptosis. This is the result of an EMT-linked remodeling of the cellular transcription factor landscape, including the repression of the gastrointestinal lineage-master regulator Klf5. Klf5 cooperates with Sox4 in oncogenesis and prevents Sox4-induced apoptosis. Smad4 is required for EMT but dispensable for Sox4 induction by TGF-β. TGF-β-induced Sox4 is thus geared to bolster progenitor identity, while simultaneous Smad4-dependent EMT strips Sox4 of an essential partner in oncogenesis. Our work demonstrates that TGF-β tumor suppression functions through an EMT-mediated disruption of a lineage-specific transcriptional network.
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Cites
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Cited by
Nieto, M. A., Huang, R. Y.-J., Jackson, R. A., & Thiery, J. P. (2016) · Cell · doi:10.1016/j.cell.2016.06.028 · Cited by 4,492
Transforming Growth Factor-β Signaling in Immunity and Cancer
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Self-citationRecovering Gene Interactions from Single-Cell Data Using Data Diffusion
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Metadata
- Authors
- David, C. J., Huang, Y.-H., Chen, M., Su, J., Zou, Y., Bardeesy, N., Iacobuzio-Donahue, C. A., & Massagué, J.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 164
- Issue
- 5
- Pages
- 1015-1030
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2280923709
- Cited by
- 593
- References
- 60
- FWCI
- 30.25
- Type
- journal article
- Language
- en
- Open access
- bronze
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