ArticleProceedings of the National Academy of Sciences of the United States of America2012
Splicing program of human MENA produces a previously undescribed isoform associated with invasive, mesenchymal-like breast tumors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- The possible role of Mena protein and its splicing-derived variants in embryogenesis, carcinogenesis, and tumor invasion: a systematic review of the literature.BioMed research international · 2013Pooled it
- RNA splicing in health and disease.Molecular biomedicine · 2026Review
- Challenges and advances in drug resistance and tolerance in cancer.Journal of experimental & clinical cancer research : CR · 2026Review
- Long non-coding RNA H19 transported by colorectal cancer small extracellular vesicles promotes alternative splicing in healthy hepatocytes: new insights on liver pre-metastatic niche formation.Cell communication and signaling : CCS · 2026Article
- Reciprocal regulation of hMENA and TGF-β signaling in cancer-associated fibroblasts promotes EMT, immunosuppression, poor prognosis, and ICT resistance in NSCLC.Journal for immunotherapy of cancer · 2026Article
- Alternative Splicing in Embryo Implantation.Maternal-fetal medicine (Wolters Kluwer Health, Inc.) · 2025Review
- The splicing machinery is dysregulated and represents a therapeutic vulnerability in breast cancer.Cellular and molecular life sciences : CMLS · 2024Article
- Upregulation of ENAH by a PI3K/AKT/β-catenin cascade promotes oral cancer cell migration and growth via an ITGB5/Src axis.Cellular & molecular biology letters · 2024Article
- Mammalian enabled protein enhances tamoxifen sensitivity of the hormone receptor-positive breast cancer patients by suppressing the AKT signaling pathway.Biology direct · 2024Article
- RBFOX2 as a regulatory linchpin in cancer: insights from a comprehensive review of its roles in tumorigenesis.American journal of cancer research · 2024Review
- Role of epithelial splicing regulatory protein 1 in cancer progression.Cancer cell international · 2023Review
- hMENA isoforms regulate cancer intrinsic type I IFN signaling and extrinsic mechanisms of resistance to immune checkpoint blockade in NSCLC.Journal for immunotherapy of cancer · 2023Article
- Review
- Matrix stiffness regulates tumor cell intravasation through expression and ESRP1-mediated alternative splicing of MENA.Cell reports · 2023Article
- Mena regulates nesprin-2 to control actin-nuclear lamina associations, trans-nuclear membrane signalling and gene expression.Nature communications · 2023Article
- RNA splicing dysregulation and the hallmarks of cancer.Nature reviews. Cancer · 2023Review
- Epigenetic reprogramming in pancreatic premalignancy and clinical implications.Frontiers in oncology · 2023Review
- Characterization of alternative mRNA splicing in cultured cell populations representing progressive stages of human fetal kidney development.Scientific reports · 2022Article
- Underlying mechanisms of epithelial splicing regulatory proteins in cancer progression.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Integration of TE Induces Cancer Specific Alternative Splicing Events.International journal of molecular sciences · 2022Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Human mena (hMENA), a member of the actin cytoskeleton regulators Ena/VASP, is overexpressed in high-risk preneoplastic lesions and in primary breast tumors and has been identified as playing a role in invasiveness and poor prognosis in breast cancers that express HER2. Here we identify a unique isoform, hMENAΔv6, derived from the hMENA alternative splicing program. In an isogenic model of human breast cancer progression, we show that hMENA(11a) is expressed in premalignant cells, whereas hMENAΔv6 expression is restricted to invasive cancer cells. "Reversion" of the malignant phenotype leads to concurrent down-regulation of all hMENA isoforms. In breast cancer cell lines, isoform-specific hMENA overexpression or knockdown revealed that in the absence of hMENA(11a), overexpression of hMENAΔv6 increased cell invasion, whereas overexpression of hMENA(11a) reduced the migratory and invasive ability of these cells. hMENA(11a) splicing was shown to be dependent on the epithelial regulator of splicing 1 (ESRP1), and forced expression of ESRP1 in invasive mesenchymal breast cancer cells caused a phenotypic switch reminiscent of a mesenchymal-to-epithelial transition (MET) characterized by changes in the cytoskeletal architecture, reexpression of hMENA(11a), and a reduction in cell invasion. hMENA-positive primary breast tumors, which are hMENA(11a)-negative, are more frequently E-cadherin low in comparison with tumors expressing hMENA(11a). These data suggest that polarized and growth-arrested cellular architecture correlates with absence of alternative hMENA isoform expression, and that the hMENA splicing program is relevant to malignant progression in invasive disease.
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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.