ArticleBMC cancer2012
Downregulation of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) in human hepatocellular carcinoma and their prognostic significance.
Article in BMC cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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55 citing papers in PubMed, 108 citations in OpenAlex.
- Cell-cycle reactivation and hepatocyte identity loss in hepatocellular carcinoma: Transcriptomic hallmarks and validation strategies (Review).Oncology letters · 2026Review
- Synergistic Effects of Atractylodes-Derived Sesquiterpenes and Polyacetylene on Chemotherapeutic Sensitivity in Cholangiocarcinoma: Impact on Transporter Gene Expression.Molecules (Basel, Switzerland) · 2026Article
- Cannabidiol-Ion Channel Interactions Represent a Promising Preventive and Therapeutic Strategy in Hepatocellular Carcinoma.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- Unraveling the role of the solute carrier family in hepatocellular carcinoma: mechanisms and therapeutic prospects.Cancer cell international · 2025Review
- Identifying Genes Associated with the Anticancer Activity of a Fluorinated Chalcone in Triple-Negative Breast Cancer Cells Using Bioinformatics Tools.International journal of molecular sciences · 2025Article
- Epizootic shell disease induces systemic transcriptomic shifts inFrontiers in physiology · 2025Article
- In Vitro and In Silico Studies on Cytotoxic Properties of Oxythiamine and 2'-Methylthiamine.International journal of molecular sciences · 2024Article
- Mechanisms of Sorafenib Resistance in HCC Culture Relate to the Impaired Membrane Expression of Organic Cation Transporter 1 (OCT1).Journal of hepatocellular carcinoma · 2024Article
- [Research progress on the mechanism and response strategies of molecular targeted drug resistance in liver cancer].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Article
- Article
- The Role of Organic Cation Transporters in the Pharmacokinetics, Pharmacodynamics and Drug-Drug Interactions of Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2023Review
- Aldo-keto reductase family member C3 (AKR1C3) promotes hepatocellular carcinoma cell growth by producing prostaglandin F2α.Oncology research · 2023Article
- Article
- Structural basis of organic cation transporter-3 inhibition.Nature communications · 2022Article
- Expression and clinical significance of organic cation transporter family in glioblastoma multiforme.Irish journal of medical science · 2022Article
- Identification of the Tumor Immune Microenvironment and Therapeutic Biomarkers by a Novel Molecular Subtype Based on Aging-Related Genes in Hepatocellular Carcinoma.Frontiers in surgery · 2022Article
- Computational Characterizing Necroptosis Reveals Implications for Immune Infiltration and Immunotherapy of Hepatocellular Carcinoma.Frontiers in oncology · 2022Article
- High expression of PARD3 predicts poor prognosis in hepatocellular carcinoma.Scientific reports · 2021Article
- A guide to plasma membrane solute carrier proteins.The FEBS journal · 2021Review
- Functional inhibition of Oct leads to HNF4α upregulation.Experimental and therapeutic medicine · 2021Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOrganic cation transporters (OCT) are responsible for the uptake and intracellular inactivation of a broad spectrum of endogenous substrates and detoxification of xenobiotics and chemotherapeutics. The transporters became pharmaceutically interesting, because OCTs are determinants of the cytotoxicity of platin derivates and the transport activity has been shown to correlate with the sensitivity of tumors towards tyrosine kinase inhibitors. No data exist about the relevance of OCTs in hepatocellular carcinoma (HCC).
methodsOCT1 (SLC22A1) and OCT3 (SLC22A3) mRNA expression was measured in primary human HCC and corresponding non neoplastic tumor surrounding tissue (TST) by real time PCR (n = 53). Protein expression was determined by western blot analysis and immunofluorescence. Data were correlated with the clinicopathological parameters of HCCs.
resultsReal time PCR showed a downregulation of SLC22A1 and SLC22A3 in HCC compared to TST (p ≤ 0.001). A low SLC22A1 expression was associated with a worse patient survival (p < 0.05). Downregulation was significantly associated with advanced HCC stages, indicated by a higher number of T3 tumors (p = 0.025) with a larger tumor diameter (p = 0.035), a worse differentiation (p = 0.001) and higher AFP-levels (p = 0.019). In accordance, SLC22A1 was less frequently downregulated in tumors with lower stages who underwent transarterial chemoembolization (p < 0.001) and liver transplantation (p = 0.001). Tumors with a low SLC22A1 expression (< median) showed a higher SLC22A3 expression compared to HCC with high SLC22A1 expression (p < 0.001). However, there was no significant difference in tumor characteristics according to the level of the SLC22A3 expression.In the western blot analysis we found a different protein expression pattern in tumor samples with a more diffuse staining in the immunofluorescence suggesting that especially OCT1 is not functional in advanced HCC.
conclusionThe downregulation of OCT1 is associated with tumor progression and a worse patient survival.
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