ArticleMolecular cancer2014
SAP domain-dependent Mkl1 signaling stimulates proliferation and cell migration by induction of a distinct gene set indicative of poor prognosis in breast cancer patients.
Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 60 citations in OpenAlex.
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- Biofunctionalization of Collagen Barrier Membranes with Bone-Conditioned Medium, as a Natural Source of Growth Factors, Enhances Osteoblastic Cell Behavior.International journal of molecular sciences · 2025Article
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- mDia2 is an important mediator of MRTF-A-dependent regulation of breast cancer cell migration.Molecular biology of the cell · 2024Article
- Differential molecular profiles and associated functionalities characterize connective tissue grafts obtained at different locations and depths in the human palate.International journal of oral science · 2023Article
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- Activation of an actin signaling pathway in pre-malignant mammary epithelial cells by P-cadherin is essential for transformation.Disease models & mechanisms · 2023Article
- MKL-1-induced PINK1-AS overexpression contributes to the malignant progression of hepatocellular carcinoma via ALDOA-mediated glycolysis.Scientific reports · 2022Article
- Advances on the roles of tenascin-C in cancer.Journal of cell science · 2022Article
- Myocardin-related transcription factor's interaction with serum-response factor is critical for outgrowth initiation, progression, and metastatic colonization of breast cancer cells.FASEB bioAdvances · 2022Article
- Ultrasound microbubble-mediated RNA interference targeting WNT1 inducible signaling pathway protein 1(WISP1) suppresses the proliferation and metastasis of breast cancer cells.Bioengineered · 2022Article
- Lamina-associated polypeptide 2α is required for intranuclear MRTF-A activity.Scientific reports · 2022Article
- A Novel Volume-Stable Collagen Matrix Induces Changes in the Behavior of Primary Human Oral Fibroblasts, Periodontal Ligament, and Endothelial Cells.International journal of molecular sciences · 2021Article
- Cellular responses to deproteinized bovine bone mineral biofunctionalized with bone-conditioned medium.Clinical oral investigations · 2021Article
- NG2/CSPG4, CD146/MCAM and VAP1/AOC3 are regulated by myocardin-related transcription factors in smooth muscle cells.Scientific reports · 2021Article
- Positive Effects of Three-Dimensional Collagen-Based Matrices on the Behavior of Osteoprogenitors.Frontiers in bioengineering and biotechnology · 2021Article
- Role of hyaluronan in regulating self-renewal and osteogenic differentiation of mesenchymal stromal cells and pre-osteoblasts.Clinical oral investigations · 2020Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe main cause of death of breast cancer patients is not the primary tumor itself but the metastatic disease. Identifying breast cancer-specific signatures for metastasis and learning more about the nature of the genes involved in the metastatic process would 1) improve our understanding of the mechanisms of cancer progression and 2) reveal new therapeutic targets. Previous studies showed that the transcriptional regulator megakaryoblastic leukemia-1 (Mkl1) induces tenascin-C expression in normal and transformed mammary epithelial cells. Tenascin-C is known to be expressed in metastatic niches, is highly induced in cancer stroma and promotes breast cancer metastasis to the lung.
methodsUsing HC11 mammary epithelial cells overexpressing different Mkl1 constructs, we devised a subtractive transcript profiling screen to identify the mechanism by which Mkl1 induces a gene set co-regulated with tenascin-C. We performed computational analysis of the Mkl1 target genes and used cell biological experiments to confirm the effect of these gene products on cell behavior. To analyze whether this gene set is prognostic of accelerated cancer progression in human patients, we used the bioinformatics tool GOBO that allowed us to investigate a large breast tumor data set linked to patient data.
resultsWe discovered a breast cancer-specific set of genes including tenascin-C, which is regulated by Mkl1 in a SAP domain-dependent, serum response factor-independent manner and is strongly implicated in cell proliferation, cell motility and cancer. Downregulation of this set of transcripts by overexpression of Mkl1 lacking the SAP domain inhibited cell growth and cell migration. Many of these genes are direct Mkl1 targets since their promoter-reporter constructs were induced by Mkl1 in a SAP domain-dependent manner. Transcripts, most strongly reduced in the absence of the SAP domain were mechanoresponsive. Finally, expression of this gene set is associated with high-proliferative poor-outcome classes in human breast cancer and a strongly reduced survival rate for patients independent of tumor grade.
conclusionsThis study highlights a crucial role for the transcriptional regulator Mkl1 and its SAP domain during breast cancer progression. We identified a novel gene set that correlates with bad prognosis and thus may help in deciding the rigor of therapy.
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