ArticleMolecular cancer2011
Cyclophilin A enhances cell proliferation and tumor growth of liver fluke-associated cholangiocarcinoma.
Article in Molecular cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 58 citations in OpenAlex.
- Single-cell analyses reveal metastasis mechanism and microenvironment remodeling of lymph node in intrahepatic cholangiocarcinoma.JHEP reports : innovation in hepatology · 2025Article
- SHCBP1 drives tumor progression in triple-negative breast cancer.Frontiers in oncology · 2025Article
- Cyclosporin A-Based PROTACs Can Deplete Abundant Cellular Cyclophilin A without Suppressing T Cell Activation.Molecules (Basel, Switzerland) · 2024Article
- PPIA dictates NRF2 stability to promote lung cancer progression.Nature communications · 2024Article
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- Structure/epitope analysis and IgE binding activities of three cyclophilin family proteins from Dermatophagoides pteronyssinus.Scientific reports · 2023Article
- CD147 and cyclophilin A: a promising potential targeted therapy for COVID-19 and associated cancer progression and chemo-resistance.Infectious agents and cancer · 2023Article
- Cyclophilin A/CD147 Interaction: A Promising Target for Anticancer Therapy.International journal of molecular sciences · 2022Review
- Microplitis bicoloratus bracovirus regulates cyclophilin A-apoptosis-inducing factor interaction to induce cell apoptosis in the insect immunosuppressive process.Archives of insect biochemistry and physiology · 2022Article
- Review
- Liver fluke granulin promotes extracellular vesicle-mediated crosstalk and cellular microenvironment conducive to cholangiocarcinoma.Neoplasia (New York, N.Y.) · 2020Article
- Chromomycin A3 suppresses cholangiocarcinoma growth by induction of S phase cell cycle arrest and suppression of Sp1‑related anti‑apoptotic proteins.International journal of molecular medicine · 2020Article
- CD147 augmented monocarboxylate transporter-1/4 expression through modulation of the Akt-FoxO3-NF-κB pathway promotes cholangiocarcinoma migration and invasion.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- Oxidized low-density lipoprotein inhibits the degradation of cyclophilin A via the lysosome in vascular smooth muscle cells.American journal of translational research · 2020Article
- Citron Rho-Interacting Serine/Threonine Kinase Promotes HIF1a-CypA Signaling and Growth of Human Pancreatic Adenocarcinoma.BioMed research international · 2020Article
- Role of CyPA in cardiac hypertrophy and remodeling.Bioscience reports · 2019Review
- Genomic Profiling of Biliary Tract Cancer Cell Lines Reveals Molecular Subtypes and Actionable Drug Targets.iScience · 2019Article
- Animal models of cholangiocarcinoma.Biochimica et biophysica acta. Molecular basis of disease · 2019Review
- Etoposide radiosensitizes p53-defective cholangiocarcinoma cell lines independent of their GOncology letters · 2018Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundCyclophilin A (CypA) expression is associated with malignant phenotypes in many cancers. However, the role and mechanisms of CypA in liver fluke-associated cholangiocarcinoma (CCA) are not presently known. In this study, we investigated the expression of CypA in CCA tumor tissues and CCA cell lines as well as regulation mechanisms of CypA in tumor growth using CCA cell lines.
methodsCypA expression was determined by real time RT-PCR, Western blot or immunohistochemistry. CypA silence or overexpression in CCA cells was achieved using gene delivery techniques. Cell proliferation was assessed using MTS assay or Ki-67 staining. The effect of silencing CypA on CCA tumor growth was determined in nude mice. The effect of CypA knockdown on ERK1/2 activation was assessed by Western blot.
resultsCypA was upregulated in 68% of CCA tumor tissues. Silencing CypA significantly suppressed cell proliferation in several CCA cell lines. Likewise, inhibition of CypA peptidyl-prolyl cis-trans isomerase (PPIase) activity using cyclosporin A (CsA) decreased cell proliferation. In contrast, overexpression of CypA resulted in 30% to 35% increases in proliferation of CCA cell lines. Interestingly, neither silence nor overexpression of CypA affected cell proliferation of a non-tumor human cholangiocyte cell line, MMNK1. Suppression of CypA expression attenuated ERK1/2 activity in CCA M139 cells by using both transient and stable knockdown methods. In the in vivo study, there was a 43% reduction in weight of tumors derived from CypA-silenced CCA cell lines compared with control vector CCA tumors in mice; these tumors with stable CypA silencing showed a reduced cell proliferation.
conclusionsCypA is upregulated in majority of CCA patients' tissues and confers a significant growth advantage in CCA cells. Suppression of CypA expression decreases proliferation of CCA cell lines in vitro and reduces tumor growth in the nude mouse model. Inhibition of CypA activity also reduces CCA cell proliferation. The ERK1/2 pathway may be involved in the CypA-mediated CCA cell proliferation. Thus, CypA may represent an important new therapeutic target for liver fluke-associated CCA.
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