ArticleThe Journal of pathology2015
DMP1β, a splice isoform of the tumour suppressor DMP1 locus, induces proliferation and progression of breast cancer.
Article in The Journal of pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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.
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Who cites it
30 citing papers in PubMed, 35 citations in OpenAlex.
- Oncogenic DMTF1β promotes cancer cell motility by regulating autophagy through ULK1 stabilization.Molecular oncology · 2026Article
- Intratumor microbiota Delftialacustiris correlated with METTL3 to control development of papillary thyroid carcinoma.Cancer cell international · 2026Article
- Review
- Antisense Oligonucleotide-Mediated Splice Switching: Potential Therapeutic Approach for Cancer Mitigation.Cancers · 2021Review
- SRSF5 regulates alternative splicing ofRNA biology · 2021Article
- Mechanisms regulating DMTF1β/γ expression and their functional interplay with DMTF1α.International journal of oncology · 2021Article
- Survival of Lung Cancer Patients Dependent on the LOH Status forInternational journal of molecular sciences · 2020Article
- Post-Translational Regulation of ARF: Perspective in Cancer.Biomolecules · 2020Review
- Transcription Factors in Cancer: When Alternative Splicing Determines Opposite Cell Fates.Cells · 2020Review
- Identification of Potential Prognostic Biomarkers for Breast Cancer Based on lncRNA-TF-Associated ceRNA Network and Functional Module.BioMed research international · 2020Article
- Recombinant human dentin matrix protein 1 (DMP1) induces the osteogenic differentiation of human periodontal ligament cells.Biotechnology reports (Amsterdam, Netherlands) · 2019Article
- c-MYB and DMTF1 in Cancer.Cancer investigation · 2019Review
- Aberrant RNA Splicing in Cancer and Drug Resistance.Cancers · 2018Review
- Translocations involving ETS family proteins in human cancer.Integrative cancer science and therapeutics · 2018Article
- Tumor suppression by the EGR1, DMP1, ARF, p53, and PTEN Network.Cancer investigation · 2018Article
- Aberrant expression of ETS1 and ETS2 proteins in cancer.Cancer reports and reviews · 2018Article
- Aging Mouse Models Reveal Complex Tumor-Microenvironment Interactions in Cancer Progression.Frontiers in cell and developmental biology · 2018Review
- Alternative Splicing in Breast Cancer and the Potential Development of Therapeutic Tools.Genes · 2017Review
- Stabilization of the p53-DNA Complex by the Nuclear Protein Dmp1α.Cancer investigation · 2017Article
- From General Aberrant Alternative Splicing in Cancers and Its Therapeutic Application to the Discovery of an Oncogenic DMTF1 Isoform.International journal of molecular sciences · 2017Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Our recent work has indicated that the DMP1 locus on 7q21, encoding a haplo-insufficient tumour suppressor, is hemizygously deleted at a high frequency in breast cancer. The locus encodes DMP1α protein, an activator of the p53 pathway leading to cell cycle arrest and senescence, and two other functionally undefined isoforms, DMP1β and DMP1γ. In this study, we show that the DMP1 locus is alternatively spliced in ∼30% of breast cancer cases with relatively decreased DMP1α and increased DMP1β expression. RNA-seq analyses of a publicly available database showed significantly increased DMP1β mRNA in 43-55% of human breast cancers, dependent on histological subtypes. Similarly, DMP1β protein was found to be overexpressed in ∼60% of tumours relative to their surrounding normal tissue. Importantly, alteration of DMP1 splicing and DMP1β overexpression were associated with poor clinical outcomes of the breast cancer patients, indicating that DMP1β may have a biological function. Indeed, DMP1β increased proliferation of non-tumourigenic mammary epithelial cells and knockdown of endogenous DMP1 inhibited breast cancer cell growth. To determine DMP1β's role in vivo, we established MMTV-DMP1β transgenic mouse lines. DMP1β overexpression was sufficient to induce mammary gland hyperplasia and multifocal tumour lesions in mice at 7-18 months of age. The tumours formed were adenosquamous carcinomas with evidence of transdifferentiation and keratinized deposits. Overall, we identify alternative splicing as a mechanism utilized by cancer cells to modulate the DMP1 locus through diminishing DMP1α tumour suppressor expression, while simultaneously up-regulating the tumour-promoting DMP1β isoform.
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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.