Journal article
Extracellular matrix 1 (ECM1) regulates the actin cytoskeletal architecture of aggressive breast cancer cells in part via S100A4 and Rho-family GTPases
Clinical & experimental metastasis, Vol.34(1), pp.37-49
01/2017
DOI: 10.1007/s10585-016-9827-5
PMCID: PMC5288287
PMID: 27770373
Abstract
ECM1 overexpression is an independent predictor of poor prognosis in primary breast carcinomas, however the mechanisms by which ECM1 affects tumor progression have not been completely elucidated. ECM1 was silenced in the triple-negative breast cancer cell lines Hs578T and MDAMB231 using siRNA and the cells were evaluated for changes in morphology, migration, invasion and adhesion. Actin cytoskeleton alterations were evaluated by fluorescent staining and levels of activated Rho GTPases by pull down assays. ECM1 downregulation led to significantly diminished cell migration (p = 0.0005 for Hs578T and p = 0.02 for MDAMB231) and cell adhesion (p < 0.001 for Hs578T and p = 0.01 for MDAMB231). Cell invasion (matrigel) was reduced only in the Hs578T cells (p < 0.01). Silencing decreased the expression of the prometastatic molecules S100A4 and TGFβR2 in both cell lines and CD44 in Hs578T cells. ECM1-silenced cells also exhibited alterations in cell shape and showed bundles of F-actin across the cell (stress fibers) whereas NT-siRNA treated cells showed peripheral membrane ruffling. Downregulation of ECM1 was also associated with an increased F/G actin ratio, when compared to the cells transfected with NT siRNA (p < 0.001 for Hs578T and p < 0.00035 for MDAMB231) and a concomitant decline of activated Rho A in the Hs578T cells. Re-expression of S100A4 in ECM1-silenced cells rescued the phenotype in the Hs578T cells but not the MDAMB231 cells. We conclude that ECM1 is a key player in the metastatic process and regulates the actin cytoskeletal architecture of aggressive breast cancer cells at least in part via alterations in S100A4 and Rho A.
Details
- Title: Subtitle
- Extracellular matrix 1 (ECM1) regulates the actin cytoskeletal architecture of aggressive breast cancer cells in part via S100A4 and Rho-family GTPases
- Creators
- P Gómez-Contreras - Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, University of Iowa, 200 Hawkins Drive, 4641 JCP, Iowa City, IA, 52242, USAJ M Ramiro-Díaz - Department of Physiology, Georgia Regents University, Augusta, GA, USAA Sierra - Department of Internal Medicine, University of Iowa, Iowa City, IA, USAC Stipp - Department of Biology, University of Iowa, Iowa City, IA, USAF E Domann - Free Radical and Radiation Biology, University of Iowa, Iowa City, IA, USAR J Weigel - Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, University of Iowa, 200 Hawkins Drive, 4641 JCP, Iowa City, IA, 52242, USAG Lal - Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, University of Iowa, 200 Hawkins Drive, 4641 JCP, Iowa City, IA, 52242, USA. Geeta-lal@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Clinical & experimental metastasis, Vol.34(1), pp.37-49
- DOI
- 10.1007/s10585-016-9827-5
- PMID
- 27770373
- PMCID
- PMC5288287
- NLM abbreviation
- Clin Exp Metastasis
- ISSN
- 0262-0898
- eISSN
- 1573-7276
- Publisher
- Springer Science and Business Media LLC; Netherlands
- Grant note
- K08 CA151658 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 01/2017
- Academic Unit
- Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Pathology; Surgery; Biology; Radiation Oncology; Biochemistry and Molecular Biology
- Record Identifier
- 9983991965202771
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