ArticleOncogene2012
Somatic LMCD1 mutations promoted cell migration and tumor metastasis in hepatocellular carcinoma.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Critical Role of LMCD1 in Promoting Profibrotic Characteristics of Lung Myofibroblasts in Experimental and Scleroderma-Associated Lung Fibrosis.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- RHO GTPase family in hepatocellular carcinoma.Experimental hematology & oncology · 2022Review
- KIF2C: a novel link between Wnt/β-catenin and mTORC1 signaling in the pathogenesis of hepatocellular carcinoma.Protein & cell · 2021Article
- Rac1, A Potential Target for Tumor Therapy.Frontiers in oncology · 2021Review
- Myristoylation of LMCD1 Leads to Its Species-Specific Derepression of E2F1 and NFATc1 in the Modulation of CDC6 and IL-33 Expression During Development of Vascular Lesions.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- LIM and cysteine-rich domains 1 (LMCD1) regulates skeletal muscle hypertrophy, calcium handling, and force.Skeletal muscle · 2019Article
- LMCD1 promotes osteogenic differentiation of human bone marrow stem cells by regulating BMP signaling.Cell death & disease · 2019Article
- Identification of Crucial Candidate Genes and Pathways in Glioblastoma Multiform by Bioinformatics Analysis.Biomolecules · 2019Article
- A meta-analysis of transcriptome datasets characterizes malignant transformation from melanocytes and nevi to melanoma.Oncology letters · 2018Article
- An emerging link between LIM domain proteins and nuclear receptors.Cellular and molecular life sciences : CMLS · 2018Review
- Multifocal demyelinating motor neuropathy and hamartoma syndrome associated with a de novoNeurology · 2018Article
- BAG3 Overexpression and Cytoprotective Autophagy Mediate Apoptosis Resistance in Chemoresistant Breast Cancer Cells.Neoplasia (New York, N.Y.) · 2018Article
- Article
- Transcriptome profiling reveals novel gene expression signatures and regulating transcription factors of TGFβ-induced epithelial-to-mesenchymal transition.Cancer medicine · 2016Article
- Genetic association analyses highlight biological pathways underlying mitral valve prolapse.Nature genetics · 2015Article
- Identification of New Potential Interaction Partners for Human Cytoplasmic Copper Chaperone Atox1: Roles in Gene Regulation?International journal of molecular sciences · 2015Article
- Tissue factor expressed by circulating cancer cell-derived microparticles drastically increases the incidence of deep vein thrombosis in mice.Journal of thrombosis and haemostasis : JTH · 2015Article
- Leukocytes as carriers for targeted cancer drug delivery.Expert opinion on drug delivery · 2015Review
- Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis.Disease markers · 2015Article
- Simplifying the complexity of resistance heterogeneity in metastasis.Trends in molecular medicine · 2014Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Common genetic alteration in cancer genomes is implicated for embracing an aberrant cancer gene participated in tumor progression. In this study, we identified a somatic mutated LIM and cysteine-rich domains-1 (LMCD1) as a putative metastatic oncogene in human hepatocellular carcinoma (HCC) using integrated genomic approaches. In addition to revealing genomic amplification and gene upregulation, we identified recurrent E135K (3/48 cases) mutations in HCC tissues and K237R mutation in the PLC/PRF/5 HCC cell line. Expression of mutant LMCD1 E135K or K237R reduced the stress fiber assembly, increased cortical actin accumulation and induced lamellipodial extension. Consistently, these mutations enhanced cell migration and showed activation of the Rac1-signaling pathway. Inhibition of the LMCD1/Rac1 pathway by an LMCD1 short-hairpin RNA (shLMCD1) or the Rac1 inhibitor NSC23766 suppressed the mutation-mediated lamellipodial protrusion and cell migration. In PLC/PRF/5 cells with endogenous K237R mutation, cell migration was enhanced by estrogen-induced LMCD1 expression but reversed by shLMCD1 treatment. Moreover, overexpression of LMCD1 E135K mutation significantly promoted systemic lung metastasis in a murine tail vein injection model. Together, our results suggest that LMCD1 mutations are potential oncogenic events in HCC metastasis to promote cell migration through the Rac1-signaling pathway.
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