ArticleThe Journal of clinical investigation2009
Human four-and-a-half LIM family members suppress tumor cell growth through a TGF-beta-like signaling pathway.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- Genetics of breast cancer bone metastasis: a sequential multistep pattern.Clinical & experimental metastasis · 2014Pooled it
- HCMV encoded UL84 hijacks FHL2 to suppress type I interferon production and enhance viral replication.PLoS pathogens · 2026Article
- Cardiac LIM Protein, Kidney Fibrosis, and Vascular Change after Acute Cardiorenal Syndrome.Journal of the American Society of Nephrology : JASN · 2025Article
- Immune-related gene expression with colorectal cancer risk: a Mendelian randomization analysis.Discover oncology · 2025Article
- FHL1 as a prognostic biomarker and therapeutic target in acute promyelocytic leukaemia.Discover oncology · 2025Article
- Role of four and a half LIM domain protein 1 in tumors (Review).Oncology letters · 2025Review
- FHL2 in arterial medial calcification in chronic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Article
- Loss of SREBP-1c ameliorates iron-induced liver fibrosis by decreasing lipocalin-2.Experimental & molecular medicine · 2024Article
- FHL2 promotes the aggressiveness of lung adenocarcinoma by inhibiting autophagy via activation of the PI3K/AKT/mTOR pathway.Thoracic cancer · 2024Article
- The roles of FHL2 as a mechanotransducer for cellular functions in the mechanical environment.Frontiers in cell and developmental biology · 2024Review
- The roles of FHL2 in cancer.Clinical and experimental medicine · 2023Review
- Tea domain transcription factor TEAD4 mitigates TGF-β signaling and hepatocellular carcinoma progression independently of YAP.Journal of molecular cell biology · 2023Article
- High-throughput proteomics profiling-derived signature associated with chemotherapy response and survival for stage II/III colorectal cancer.NPJ precision oncology · 2023Article
- Upregulation of the Four and a Half LIM Domains 1 linked with familial venous dysplasia in a familial genetic examination.American journal of translational research · 2023Article
- PCLassoLog: A protein complex-based, group Lasso-logistic model for cancer classification and risk protein complex discovery.Computational and structural biotechnology journal · 2023Article
- FHL1 Overexpression as A Inhibitor of Lung Cancer Cell Invasion via Increasing RhoGDIß mRNA Expression.Cell journal · 2022Article
- Review
- Function of BCLAF1 in human disease.Oncology letters · 2022Review
- The Roles of FHL3 in Cancer.Frontiers in oncology · 2022Review
- The Potential Role of Exosomal Proteins in Prostate Cancer.Frontiers in oncology · 2022Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The four-and-a-half LIM (FHL) proteins belong to a family of LIM-only proteins that regulate cell proliferation, differentiation, and apoptosis. The exact functions of each FHL protein in cancer development and progression remain unknown. Here we report that FHL1, FHL2, and FHL3 physically and functionally interact with Smad2, Smad3, and Smad4, important regulators of cancer development and progression, in a TGF-beta-independent manner. Casein kinase 1delta, but not the TGF-beta receptor, was required for the FHL-mediated TGF-beta-like responses, including increased phosphorylation of Smad2/3, interaction of Smad2/3 and Smad4, nuclear accumulation of Smad proteins, activation of the tumor suppressor gene p21, and repression of the oncogene c-myc. FHL1-3 inhibited anchorage-dependent and -independent growth of a human hepatoma cell line in vitro and tumor formation in nude mice. Further analysis of clinical samples revealed that FHL proteins are often downregulated in hepatocellular carcinomas and that this correlates with decreased TGF-beta-like responses. By establishing a link between FHL proteins and Smad proteins, this study identifies what we believe to be a novel TGF-beta-like signaling pathway and indicates that FHL proteins may be useful molecular targets for cancer therapy.
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Registered trials
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.