ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2014
SMAD4 is a potential prognostic marker in human breast carcinomas.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 21 citations in OpenAlex.
- Suppression of TRIM33 and SMAD4 Indicates a Possible Tumor-Suppressive Role in Esophageal Squamous Cell Carcinoma.Digestive diseases and sciences · 2026Article
- Multi-omic Profiling of Recurrence Risk Across Breast Cancer Subtypes.medRxiv : the preprint server for health sciences · 2026Article
- Clinical impact of the methylation status of SMAD4 and AKR1B1 genes in a liquid biopsy sample as a prognostic marker for breast cancer.Scientific reports · 2026Article
- Ivermectin inhibits ER, HER2, and TGF-β pathways in ER-positive and endocrine-resistant breast cancer cells.PloS one · 2026Article
- Drug Repurposing of Selected Antibiotics: An Emerging Approach in Cancer Drug Discovery.ACS omega · 2024Review
- Prognostic and diagnostic values of non-coding RNAs as biomarkers for breast cancer: An umbrella review and pan-cancer analysis.Frontiers in molecular biosciences · 2023Article
- Investigation of the efficacy of paclitaxel on some miRNAs profiles in breast cancer stem cells.Turkish journal of biology = Turk biyoloji dergisi · 2021Article
- Genetic ablation of pregnancy zone protein promotes breast cancer progression by activating TGF-β/SMAD signaling.Breast cancer research and treatment · 2021Article
- OXPHOS-dependent metabolic reprogramming prompts metastatic potential of breast cancer cells under osteogenic differentiation.British journal of cancer · 2020Article
- Bayesian model of signal rewiring reveals mechanisms of gene dysregulation in acquired drug resistance in breast cancer.PloS one · 2017Article
- Smad3 and phospho-Smad3 are potential markers of invasive nonfunctioning pituitary adenomas.OncoTargets and therapy · 2016Article
- Genomic aberrations in young and elderly breast cancer patients.BMC medicine · 2015Article
- Carcinosarcoma with Choriocarcinomatous and Osteosarcomatous Differentiation in a Patient with Juvenile Polyposis Syndrome.Rare tumors · 2015Article
- Hsa-miR-301a-3p Acts as an Oncogene in Laryngeal Squamous Cell Carcinoma via Target Regulation of Smad4.Journal of Cancer · 2015Article
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9 authors at 4 institutions in 2 countries.
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Abstract
SMAD4 is a downstream mediator of transforming growth factor beta. While its tumor suppressor function has been investigated as a prognostic biomarker in several human malignancies, its role as a prognostic marker in breast carcinoma is still undefined. We investigated SMAD4 expression in breast carcinoma samples of different histologic grades to evaluate the association between SMAD4 and outcome in breast cancer. We also investigated the role of SMAD4 expression status in MDA-MB-468 breast cancer cells in responding to TGF-β stimulation. SMAD4 expression was assessed in 53 breast ductal carcinoma samples and in the surrounding normal tissue from 50 of the samples using immunohistochemistry, Western blot, and real-time PCR. TGF-β-SMAD and non-SMAD signaling was assessed by Western blot in MDA-MB-468 cells with and without SMAD4 restoration. SMAD4 expression was reduced in ductal breast carcinoma as compared to surrounding uninvolved ductal breast epithelia (p < 0.05). SMAD4 expression levels decreased from Grade 1 to Grade 3 ductal breast carcinoma as assessed by immunohistochemistry (p < 0.05). Results were recapitulated by tissue array. In addition, immunohistochemistry results were further confirmed at the protein and mRNA level. We then found that non-SMAD MEK/MAPK signaling was significantly different between SMAD4 expressing MDA-MB-468 cells and SMAD4-null MDA-MB-468 cells. This is the first study indicating that SMAD4 plays a key role in shifting MAPK signaling. Further, we have demonstrated that SMAD4 has a potential role in the development of breast carcinoma and SMAD4 was a potential prognostic marker of breast carcinoma. Our findings further support the role of SMAD4 in breast carcinoma development. In addition, we observed an inverse relationship between SMAD4 levels and breast carcinoma histological grade. Our finding indicated that SMAD4 expression level in breast cancer cells played a role in responding non-SMAD signaling but not the canonic SMAD signaling. Further mechanistic studies are necessary to establish the role of SMAD4 in breast carcinoma prognosis and potential specific targeting.
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