ArticleCancer research2007
Smad4 regulates claudin-1 expression in a transforming growth factor-beta-independent manner in colon cancer cells.
Article in Cancer research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 75 citations in OpenAlex.
- Targeting claudins in cancer.Nature reviews. Drug discovery · 2026Review
- TGF-β Modulated Pathways in Colorectal Cancer: New Potential Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- The Expression of the Claudin Family of Proteins in Colorectal Cancer.Biomolecules · 2024Review
- Expression patterns of claudins in cancer.Heliyon · 2023Review
- Upregulated TGF-β1 contributes to hyperglycaemia in type 2 diabetes by potentiating glucagon signalling.Diabetologia · 2023Article
- Review
- TGF-β Signaling in Metastatic Colorectal Cancer (mCRC): From Underlying Mechanism to Potential Applications in Clinical Development.International journal of molecular sciences · 2022Review
- The role and mechanism of claudins in cancer.Frontiers in oncology · 2022Review
- Colorectal Cancer-Associated Smad4 R361 Hotspot Mutations Boost Wnt/β-Catenin Signaling through Enhanced Smad4-LEF1 Binding.Molecular cancer research : MCR · 2021Article
- Article
- Silencing Smad4 attenuates sensitivity of colorectal cancer cells to cetuximab by promoting epithelial‑mesenchymal transition.Molecular medicine reports · 2019Article
- C-reactive protein promotes inflammation through TLR4/NF-κB/TGF-β pathway in HL-1 cells.Bioscience reports · 2019Article
- Article
- Epithelial Claudin Proteins and Their Role in Gastrointestinal Diseases.Journal of pediatric gastroenterology and nutrition · 2019Article
- SMAD4 Loss in Colorectal Cancer Patients Correlates with Recurrence, Loss of Immune Infiltrate, and Chemoresistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Review
- miRNA expression profiles in Smad4-positive and Smad4-negative SW620 human colon cancer cells detected by next-generation small RNA sequencing.Cancer management and research · 2018Article
- Lipopolysaccharide Mediates the Destruction of Intercellular Tight Junction among Renal Tubular Epithelial Cells via RhoT1/SMAD-4/JAM-3 Pathway.International journal of medical sciences · 2018Article
- Animal models for studying epithelial barriers in neonatal necrotizing enterocolitis, inflammatory bowel disease and colorectal cancer.Tissue barriers · 2017Review
- Smad4 suppresses the tumorigenesis and aggressiveness of neuroblastoma through repressing the expression of heparanase.Scientific reports · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
We have recently reported that the expression of a tight junction protein, claudin-1, is increased during colon carcinogenesis and particularly metastatic colorectal cancer. Manipulation of claudin-1 levels in colon cancer cells showed a positive correlation between claudin-1 expression and tumor growth and metastasis. However, the mechanisms underlying the increased claudin-1 expression in colorectal cancer remains unknown. The tumor suppressor Smad4 is a central intracellular signal transduction component of the transforming growth factor-beta (TGF-beta) family of cytokines. Loss of Smad4 protein expression is correlated with poor prognosis and is frequently observed in invasive and metastatic colorectal carcinoma. In the present study, we report an inverse relationship between Smad4 and claudin-1 expression in human colorectal carcinoma tumor samples and in human colon cancer cell lines. We found that the expression of Smad4 in Smad4-deficient but claudin-1-positive SW480 or HT29 colon cancer cell lines down-regulates claudin-1 expression through transcriptional repression by modulating beta-catenin/T-cell factor/lymphocyte enhancer factor activity. Furthermore, this Smad4-dependent inhibition of claudin-1 expression is independent of TGF-beta signaling because Smad4 expression alone is insufficient to restore TGF-beta signaling in the SW480 cells, and the selective TGF-beta receptor kinase inhibitor LY364947 did not prevent the Smad4 suppression of claudin-1 protein expression in either SW480 or HT29 cells. Taken together, these findings suggest a novel mechanism underlying Smad4 tumor-suppressive function through regulation of a potential metastatic modulator, claudin-1, in a TGF-beta-independent manner.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.