ArticleBMC cancer2010
Overexpression of S100A4 in human cancer cell lines resistant to methotrexate.
Article in BMC cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 35 citations in OpenAlex.
- Role of S100 family proteins in colorectal cancer (CRC): an overview of their potential function as new biomarkers and therapeutic agents.Expert reviews in molecular medicine · 2025Review
- Combating Methotrexate Resistance in Cancer Treatment: A Review on Navigating Pathways and Enhancing Its Efficacy With Fat-Soluble Vitamins.Scientifica · 2025Review
- Integration of scRNA-seq and bulk RNA-seq to reveal the association and potential molecular mechanisms of metabolic reprogramming regulated by lactylation and chemotherapy resistance in ovarian cancer.Frontiers in immunology · 2025Article
- S100A4 contributes to colorectal carcinoma aggressive behavior and to chemoradiotherapy resistance in locally advanced rectal carcinoma.Scientific reports · 2024Article
- Unraveling the role of long non-coding RNAs in therapeutic resistance in acute myeloid leukemia: New prospects & challenges.Non-coding RNA research · 2024Review
- S100A4 enhances protumor macrophage polarization by control of PPAR-γ-dependent induction of fatty acid oxidation.Journal for immunotherapy of cancer · 2021Article
- S100 Calcium Binding Protein Family Members Associate With Poor Patient Outcome and Response to Proteasome Inhibition in Multiple Myeloma.Frontiers in cell and developmental biology · 2021Article
- Interaction of S100A1 with LATS1 promotes cell growth through regulation of the Hippo pathway in hepatocellular carcinoma.International journal of oncology · 2018Article
- [S100A4, a potential therapeutic target on bladder cancer stem cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2017Article
- Until Death Do Us Part: Necrosis and Oxidation Promote the Tumor Microenvironment.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2016Review
- Article
- The S100A4 D10V polymorphism is related to cell migration ability but not drug resistance in gastric cancer cells.Oncology reports · 2014Article
- Article
- The redox state of cytochrome c modulates resistance to methotrexate in human MCF7 breast cancer cells.PloS one · 2013Article
- S100 proteins as diagnostic and prognostic markers in colorectal and hepatocellular carcinoma.Hepatitis monthly · 2012Article
- Upregulated FGFR1 expression is associated with the transition of hormone-naive to castrate-resistant prostate cancer.British journal of cancer · 2011Article
- Quantitative proteomic and interaction network analysis of cisplatin resistance in HeLa cells.PloS one · 2011Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMethotrexate is a chemotherapeutic drug that is used in therapy of a wide variety of cancers. The efficiency of treatment with this drug is compromised by the appearance of resistance. Combination treatments of MTX with other drugs that could modulate the expression of genes involved in MTX resistance would be an adequate strategy to prevent the development of this resistance.
methodsThe differential expression pattern between sensitive and MTX-resistant cells was determined by whole human genome microarrays and analyzed with the GeneSpring GX software package. A global comparison of all the studied cell lines was performed in order to find out differentially expressed genes in the majority of the MTX-resistant cells. S100A4 mRNA and protein levels were determined by RT-Real-Time PCR and Western blot, respectively. Functional validations of S100A4 were performed either by transfection of an expression vector for S100A4 or a siRNA against S100A4. Transfection of an expression vector encoding for beta-catenin was used to inquire for the possible transcriptional regulation of S100A4 through the Wnt pathway.
resultsS100A4 is overexpressed in five out of the seven MTX-resistant cell lines studied. Ectopic overexpression of this gene in HT29 sensitive cells augmented both the intracellular and extracellular S100A4 protein levels and caused desensitization toward MTX. siRNA against S100A4 decreased the levels of this protein and caused a chemosensitization in combined treatments with MTX. beta-catenin overexpression experiments support a possible involvement of the Wnt signaling pathway in S100A4 transcriptional regulation in HT29 cells.
conclusionsS100A4 is overexpressed in many MTX-resistant cells. S100A4 overexpression decreases the sensitivity of HT29 colon cancer human cells to MTX, whereas its knockdown causes chemosensitization toward MTX. Both approaches highlight a role for S100A4 in MTX resistance.
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