TGF-β receptor I/II trafficking and signaling at primary cilia are inhibited by ceramide to attenuate cell migration and tumor metastasis
Open accessAbstract
Ceramide forms complexes with Smad7 to inhibit cell migration–associated TGF-β–sonic hedgehog signaling in primary cilia.
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Feedback inhibitors of TGFβ/BMP signaling, including SMAD7 and SMURF1, localize to the ciliary base and restrain excessive signaling from the primary cilium.
“Conversely, feedback inhibitors of TGFβ/BMP signalling, including SMAD7 and SMURF1 265, 288, localize to the ciliary base 268, 273 and restrain excessive signalling from the primary cilium.”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [273]
The Discussion (page unavailable) reports that a ceramide–Smad7 complex inhibits TGF-β receptor trafficking and signaling at primary cilia. It does not establish that SMAD7 localizes to the ciliary base, or address SMURF1 or BMP signaling; the Introduction instead describes Smurf2. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSMURF1 negatively regulates phosphorylation of SMAD1/5/8 at primary cilia to control cell-type specification during in vivo heart development, which in Smurf1−/− mouse embryos is associated with delayed outflow tract septation.
“Finally, the E3 ubiquitin ligase SMURF1 negatively regulates phosphorylation of SMAD1/5/8 at primary cilia to control cell-type specification during in vivo heart development, which in Smurf1−/− mouse embryos is associated with delayed outflow tract septation 273.”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [273]
The Results section on ciliary trafficking addresses CerS4, Smad7, TGF-β receptors, and cancer-cell migration, not SMURF1 regulation of SMAD1/5/8 during heart development. Searches for SMURF1, Smurf1−/− embryos, and outflow tract septation found no passage addressing the claim. The available passages have no page numbers. (LLM, conf=0.76)
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References 70 · Cited by 83
- Authors
- Gencer, S., Oleinik, N., Kim, J., Panneer Selvam, S., De Palma, R., Dany, M., Nganga, R., Thomas, R. J., Senkal, C. E., Howe, P. H., & Ogretmen, B.
- Affiliations
- Medical University of South Carolina (US)
- Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 125 Ashley Avenue, Charleston, SC 29425, USA.
- Corresponding author
- Gencer, Salih
- Oleinik, Natalia
- ORCID
- Venue
- Science Signaling
- Published
- 2017-10-24
- Volume
- 10
- Issue
- 502
- ISSN
- 1937-9145 (ISSN-L)
- 1945-0877
- PMC
- PMC5818989
- OpenAlex
- W2766486963
- Cited by
- 83
- References
- 70
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 8 · 2023: 14 · 2022: 12 · 2021: 14 · 2020: 9 · 2019: 9 · 2018: 6
- FWCI
- 4.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Signaling (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (award336702, CA088932, award336703, CA173687, award336704, CA203628)
- National Institute of Dental and Craniofacial Research (award336701, DE016572)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- TGF-beta type I receptor, TGFBR2, primary cilia, ceramide, Sonic hedgehog signaling, Smoothened, Smad7, IFT88, cell migration, metastasis, liver metastasis, breast cancer, 4T1 cells, receptor trafficking
- MeSH terms
- A549 Cells, Animals, Cell Movement, Ceramides, Cilia, Disease Models, Animal, Humans, Neoplasm Metastasis, Receptors, Transforming Growth Factor beta, Mice, Knockout, Cell Line, Tumor, Cell Proliferation, Sphingosine N-Acyltransferase, Mice, Smad7 Protein, Gene Knockdown Techniques
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