miR-23b regulates cytoskeletal remodeling, motility and metastasis by directly targeting multiple transcripts
(2013) In Nucleic Acids Research 41(10). p.12-5400- Abstract
Uncontrolled cell proliferation and cytoskeletal remodeling are responsible for tumor development and ultimately metastasis. A number of studies have implicated microRNAs in the regulation of cancer cell invasion and migration. Here, we show that miR-23b regulates focal adhesion, cell spreading, cell-cell junctions and the formation of lamellipodia in breast cancer (BC), implicating a central role for it in cytoskeletal dynamics. Inhibition of miR-23b, using a specific sponge construct, leads to an increase of cell migration and metastatic spread in vivo, indicating it as a metastatic suppressor microRNA. Clinically, low miR-23b expression correlates with the development of metastases in BC patients. Mechanistically, miR-23b is able to... (More)
Uncontrolled cell proliferation and cytoskeletal remodeling are responsible for tumor development and ultimately metastasis. A number of studies have implicated microRNAs in the regulation of cancer cell invasion and migration. Here, we show that miR-23b regulates focal adhesion, cell spreading, cell-cell junctions and the formation of lamellipodia in breast cancer (BC), implicating a central role for it in cytoskeletal dynamics. Inhibition of miR-23b, using a specific sponge construct, leads to an increase of cell migration and metastatic spread in vivo, indicating it as a metastatic suppressor microRNA. Clinically, low miR-23b expression correlates with the development of metastases in BC patients. Mechanistically, miR-23b is able to directly inhibit a number of genes implicated in cytoskeletal remodeling in BC cells. Through intracellular signal transduction, growth factors activate the transcription factor AP-1, and we show that this in turn reduces miR-23b levels by direct binding to its promoter, releasing the pro-invasive genes from translational inhibition. In aggregate, miR-23b expression invokes a sophisticated interaction network that co-ordinates a wide range of cellular responses required to alter the cytoskeleton during cancer cell motility.
(Less)
- author
- publishing date
- 2013-05-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Animals, Breast Neoplasms, Cardiac Myosins, Cell Adhesion, Cell Line, Cell Line, Tumor, Cell Movement, Cytoskeletal Proteins, Cytoskeleton, Female, Focal Adhesions, Gene Expression Regulation, Neoplastic, Humans, Mice, Mice, Nude, MicroRNAs, Myosin Light Chains, Neoplasm Metastasis, Phosphorylation, Promoter Regions, Genetic, Pseudopodia, Transcription Factor AP-1, Transcription, Genetic, p21-Activated Kinases, Journal Article, Research Support, Non-U.S. Gov't
- in
- Nucleic Acids Research
- volume
- 41
- issue
- 10
- pages
- 13 pages
- publisher
- Oxford University Press
- external identifiers
-
- scopus:84878535897
- pmid:23580553
- ISSN
- 1362-4962
- DOI
- 10.1093/nar/gkt245
- language
- English
- LU publication?
- no
- id
- 93b8c64c-1aa8-4991-a577-911dc00f2b1e
- date added to LUP
- 2016-12-06 10:16:09
- date last changed
- 2024-04-05 11:54:21
@article{93b8c64c-1aa8-4991-a577-911dc00f2b1e,
abstract = {{<p>Uncontrolled cell proliferation and cytoskeletal remodeling are responsible for tumor development and ultimately metastasis. A number of studies have implicated microRNAs in the regulation of cancer cell invasion and migration. Here, we show that miR-23b regulates focal adhesion, cell spreading, cell-cell junctions and the formation of lamellipodia in breast cancer (BC), implicating a central role for it in cytoskeletal dynamics. Inhibition of miR-23b, using a specific sponge construct, leads to an increase of cell migration and metastatic spread in vivo, indicating it as a metastatic suppressor microRNA. Clinically, low miR-23b expression correlates with the development of metastases in BC patients. Mechanistically, miR-23b is able to directly inhibit a number of genes implicated in cytoskeletal remodeling in BC cells. Through intracellular signal transduction, growth factors activate the transcription factor AP-1, and we show that this in turn reduces miR-23b levels by direct binding to its promoter, releasing the pro-invasive genes from translational inhibition. In aggregate, miR-23b expression invokes a sophisticated interaction network that co-ordinates a wide range of cellular responses required to alter the cytoskeleton during cancer cell motility.</p>}},
author = {{Pellegrino, Loredana and Stebbing, Justin and Braga, Vania M and Frampton, Adam E and Jacob, Jimmy and Buluwela, Lakjaya and Jiao, Long R and Periyasamy, Manikandan and Madsen, Chris D and Caley, Matthew P and Ottaviani, Silvia and Roca-Alonso, Laura and El-Bahrawy, Mona and Coombes, R Charles and Krell, Jonathan and Castellano, Leandro}},
issn = {{1362-4962}},
keywords = {{Animals; Breast Neoplasms; Cardiac Myosins; Cell Adhesion; Cell Line; Cell Line, Tumor; Cell Movement; Cytoskeletal Proteins; Cytoskeleton; Female; Focal Adhesions; Gene Expression Regulation, Neoplastic; Humans; Mice; Mice, Nude; MicroRNAs; Myosin Light Chains; Neoplasm Metastasis; Phosphorylation; Promoter Regions, Genetic; Pseudopodia; Transcription Factor AP-1; Transcription, Genetic; p21-Activated Kinases; Journal Article; Research Support, Non-U.S. Gov't}},
language = {{eng}},
month = {{05}},
number = {{10}},
pages = {{12--5400}},
publisher = {{Oxford University Press}},
series = {{Nucleic Acids Research}},
title = {{miR-23b regulates cytoskeletal remodeling, motility and metastasis by directly targeting multiple transcripts}},
url = {{http://dx.doi.org/10.1093/nar/gkt245}},
doi = {{10.1093/nar/gkt245}},
volume = {{41}},
year = {{2013}},
}