ArticleMolecular cancer2012
Klotho-beta overexpression as a novel target for suppressing proliferation and fibroblast growth factor receptor-4 signaling in hepatocellular carcinoma.
Article in Molecular cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 71 citations in OpenAlex.
- A first-in-human phase 1/2 study of FGF401 and combination of FGF401 with spartalizumab in patients with hepatocellular carcinoma or biomarker-selected solid tumors.Journal of experimental & clinical cancer research : CR · 2022Trial
- KLB as a potential prognostic biomarker and therapeutic target in colorectal cancer: insights from multi omics and single cell analyses.Discover oncology · 2025Article
- The Impact of Klotho in Cancer: From Development and Progression to Therapeutic Potential.Genes · 2025Review
- HAND2-AS1 Promotes Ferroptosis to Reverse Lenvatinib Resistance in Hepatocellular Carcinoma by TLR4/NOX2/DUOX2 Axis.Current cancer drug targets · 2025Article
- Klotho in Cancer: Potential Diagnostic and Prognostic Applications.Diagnostics (Basel, Switzerland) · 2023Review
- Klotho-beta attenuates Rab8a-mediated exosome regulation and promotes prostate cancer progression.Oncogene · 2023Article
- A comprehensive computational analysis to explore the importance of SIGLECs in HCC biology.BMC gastroenterology · 2023Article
- Fibroblast Growth Factor 21 Response in a Preclinical Alcohol Model of Acute-on-Chronic Liver Injury.International journal of molecular sciences · 2021Article
- Role of FGF15 in Hepatic Surgery in the Presence of Tumorigenesis: Dr. Jekyll or Mr. Hyde?Cells · 2021Review
- Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling.Cells · 2021Review
- Serum β-klotho is a potential biomarker in the prediction of clinical outcomes among patients with NSCLC.Journal of thoracic disease · 2021Article
- Advances of Targeted Therapy for Hepatocellular Carcinoma.Frontiers in oncology · 2021Review
- βKlotho, a direct target of miR-206, contributes to the growth of hepatoblastoma through augmenting PI3K/Akt/mTOR signaling.American journal of cancer research · 2021Article
- The potential roles of exosomes in pancreatic cancer initiation and metastasis.Molecular cancer · 2020Review
- γ-Klotho is correlated with resistance to docetaxel in castration-resistant prostate cancer.Oncology letters · 2020Article
- Dissecting the Role of the FGF19-FGFR4 Signaling Pathway in Cancer Development and Progression.Frontiers in cell and developmental biology · 2020Review
- Functional validity, role, and implications of heavy alcohol consumption genetic loci.Science advances · 2020Article
- Klotho expression and nodal involvement as predictive factors for large cell lung carcinoma.Archives of medical science : AMS · 2019Article
- FGF19-Cells · 2019Review
- Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe had previously demonstrated overexpression of fibroblast growth factor receptor-4 (FGFR4) in hepatocellular carcinoma (HCC). However, additional molecular mechanisms resulting in amplified FGFR4 signaling in HCC remain under-studied. Here, we studied the mechanistic role of its co-receptor klotho-beta (KLB) in driving elevated FGFR4 activity in HCC progression.
resultsQuantitative real-time PCR analysis identified frequent elevation of KLB gene expression in HCC tumors relative to matched non-tumor tissue, with a more than two-fold increase correlating with development of multiple tumors in patients. KLB-silencing in Huh7 cells decreased cell proliferation and suppressed FGFR4 downstream signaling. While transient repression of KLB-FGFR4 signaling decreased protein expression of alpha-fetoprotein (AFP), a HCC diagnostic marker, prolonged inhibition enriched for resistant HCC cells exhibiting increased liver stemness.
conclusionsElevated KLB expression in HCC tissues provides further credence to the oncogenic role of increased FGFR4 signaling in HCC progression and represents a novel biomarker to identify additional patients amenable to anti-FGFR4 therapy. The restricted tissue expression profile of KLB, together with the anti-proliferative effect observed with KLB-silencing, also qualifies it as a specific and potent therapeutic target for HCC patients. The enrichment of a liver stem cell-like population in response to extended KLB-FGFR4 repression necessitates further investigation to target the development of drug resistance.
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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 Socratic graph.