ArticleBMC cell biology2012
Regulation of ROCK1 via Notch1 during breast cancer cell migration into dense matrices.
Article in BMC cell biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 1 citations in OpenAlex.
- Distinct shared and compartment-enriched oncogenic networks drive primary versus metastatic breast cancer.Nature communications · 2023Article
- Tumor-suppressing effects of miR-381-3p in pediatric acute myeloid leukemia via ROCK1 downregulation.Functional & integrative genomics · 2023Article
- LINC00491 promotes cell growth and metastasis through miR-324-5p/ROCK1 in liver cancer.Journal of translational medicine · 2021Article
- Matrix Pore Size Governs Escape of Human Breast Cancer Cells from a Microtumor to an Empty Cavity.iScience · 2020Article
- Identification of DHX36 as a tumour suppressor through modulating the activities of the stress-associated proteins and cyclin-dependent kinases in breast cancer.American journal of cancer research · 2020Article
- A review of the influence of mammographic density on breast cancer clinical and pathological phenotype.Breast cancer research and treatment · 2019Review
- Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis.Breast cancer research : BCR · 2016Article
- Stromal characteristics may hold the key to mammographic density: the evidence to date.Oncotarget · 2016Review
- Melatonin decreases breast cancer metastasis by modulating Rho-associated kinase protein-1 expression.Journal of pineal research · 2016Article
- Knockdown of Rho-associated protein kinase 1 suppresses proliferation and invasion of glioma cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Physical biology in cancer. 5. The rocky road of metastasis: the role of cytoskeletal mechanics in cell migratory response to 3D matrix topography.American journal of physiology. Cell physiology · 2014Review
- Regulation of ROCK activity in cancer.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2013Review
- ROCK1 inhibition promotes the self-renewal of a novel mouse mammary cancer stem cell.Stem cells (Dayton, Ohio) · 2013Article
- Dormant but migratory tumour cells in desmoplastic stroma of invasive ductal carcinomas.Clinical & experimental metastasis · 2012Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe behaviour of tumour cells depends on factors such as genetics and the tumour microenvironment. The latter plays a crucial role in normal mammary gland development and also in breast cancer initiation and progression. Breast cancer tissues tend to be highly desmoplastic and dense matrix as a pre-existing condition poses one of the highest risk factors for cancer development. However, matrix influence on tumour cell gene expression and behaviour such as cell migration is not fully elucidated.
resultsWe generated high-density (HD) matrices that mimicked tumour collagen content of 20 mg/cm3 that were ~14-fold stiffer than low-density (LD) matrix of 1 mg/cm3. Live-cell imaging showed breast cancer cells utilizing cytoplasmic streaming and cell body contractility for migration within HD matrix. Cell migration was blocked in the presence of both the ROCK inhibitor, Y-27632, and the MMP inhibitor, GM6001, but not by the drugs individually. This suggests roles for ROCK1 and MMP in cell migration are complicated by compensatory mechanisms. ROCK1 expression and protein activity, were significantly upregulated in HD matrix but these were blocked by treatment with a histone deacetylase (HDAC) inhibitor, MS-275. In HD matrix, the inhibition of ROCK1 by MS-275 was indirect and relied upon protein synthesis and Notch1. Inhibition of Notch1 using pooled siRNA or DAPT abrogated the inhibition of ROCK1 by MS-275.
conclusionIncreased matrix density elevates ROCK1 activity, which aids in cell migration via cell contractility. The upregulation of ROCK1 is epigenetically regulated in an indirect manner involving the repression of Notch1. This is demonstrated from inhibition of HDACs by MS-275, which caused an upregulation of Notch1 levels leading to blockade of ROCK1 expression.
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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.