ArticleEMBO molecular medicine2013
Depletion of the transcriptional coactivators megakaryoblastic leukaemia 1 and 2 abolishes hepatocellular carcinoma xenograft growth by inducing oncogene-induced senescence.
Article in EMBO molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 61 citations in OpenAlex.
- One-Pot Gateway to Quinazoline-Thiohydantoin Fused Scaffolds and Discovery of Their Antileukemic Activity.JACS Au · 2026Article
- Filamin a binds deleted in liver cancer 1 (DLC1) to promote its tumor suppressor activity and inhibit the SRF coactivator MRTF-A.Neoplasia (New York, N.Y.) · 2026Article
- MRTF-dependent cytoskeletal dynamics drive efficient cell cycle progression.Journal of cell science · 2025Article
- Identification of novel inhibitors of the transcriptional coactivator MRTF-A for HCC therapy.Molecular therapy. Oncology · 2024Article
- Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure.Acta pharmaceutica Sinica. B · 2024Article
- Curcumin improves atrial fibrillation susceptibility by regulating tsRNA expression in aging mouse atrium.PeerJ · 2024Article
- Fixing the GAP: The role of RhoGAPs in cancer.European journal of cell biology · 2022Review
- Selenocystine-Derived Label-Free Fluorescent Schiff Base Nanocomplex for siRNA Delivery Synergistically Kills Cancer Cells.Molecules (Basel, Switzerland) · 2022Article
- MKL1 regulates hepatocellular carcinoma cell proliferation, migration and apoptosis via the COMPASS complex and NF-κB signaling.BMC cancer · 2021Article
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- Review
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- Mechano-Signaling Aspects of Hepatocellular Carcinoma.Journal of Cancer · 2021Review
- The Jumonji Domain-Containing Histone Demethylase Homolog 1D/lysine Demethylase 7A (JHDM1D/KDM7A) Is an Epigenetic Activator of RHOJ Transcription in Breast Cancer Cells.Frontiers in cell and developmental biology · 2021Article
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- Nanoparticle-complexed antimiRs for inhibiting tumor growth and metastasis in prostate carcinoma and melanoma.Journal of nanobiotechnology · 2020Article
- The Role of lncRNAs TAPIR-1 and -2 as Diagnostic Markers and Potential Therapeutic Targets in Prostate Cancer.Cancers · 2020Article
- Downregulation of miR‑142‑5p inhibits human aortic smooth muscle cell proliferation and migration by targeting MKL2.Molecular medicine reports · 2020Article
- Inhibition of TRPM7 blocks MRTF/SRF-dependent transcriptional and tumorigenic activity.Oncogene · 2020Article
- MKL1 Mediates TGF-β Induced RhoJ Transcription to Promote Breast Cancer Cell Migration and Invasion.Frontiers in cell and developmental biology · 2020Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Megakaryoblastic leukaemia 1 and 2 (MKL1/2) are coactivators of the transcription factor serum response factor (SRF). Here, we provide evidence that depletion of MKL1 and 2 abolishes hepatocellular carcinoma (HCC) xenograft growth. Loss of the tumour suppressor deleted in liver cancer 1 (DLC1) and the subsequent activation of RhoA were prerequisites for MKL1/2 knockdown-mediated growth arrest. We identified oncogene-induced senescence as the molecular mechanism underlying the anti-proliferative effect of MKL1/2 knockdown. MKL1/2 depletion resulted in Ras activation, elevated p16 expression and hypophosphorylation of the retinoblastoma (Rb) protein in DLC1-deficient HCC cells. Interestingly, reconstitution of HuH7 HCC cells with DLC1 also induced senescence. Evaluation of the therapeutic efficacy of MKL1/2 knockdown in vivo revealed that systemic treatment of nude mice bearing HuH7 tumour xenografts with MKL1/2 siRNAs complexed with polyethylenimine (PEI) completely abolished tumour growth. The regression of the xenografts was associated with senescence. Importantly, PEI-complexed MKL1 siRNA alone was sufficient for complete abrogation of HCC xenograft growth. Thus, MKL1/2 represent promising novel therapeutic targets for the treatment of HCCs characterized by DLC1 loss.
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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 OpenQuestion graph.