Role of PI3K/Akt on migration and invasion of MCF10A cells treated with extracellular vesicles from MDA-MB-231 cells stimulated with linoleic acid (original) (raw)
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Extracellular vesicles (EVs) are membrane-limited vesicles secreted by normal and malignant cells and their function is dependent on the cargo they carry and the cell type from which they originate. Moreover, EVs mediate many stages of tumor progression including angiogenesis, escape from immune surveillance and extracellular matrix degradation. Linoleic acid (LA) is an essential polyunsaturated fatty acid that induces expression of plasminogen activator inhibitor-1, proliferation, migration and invasion in breast cancer cells. However the role of secreted EVs from MDA-MB-231 cells stimulated with LA like mediator of the epithelial-mesenchymal-transition (EMT) process in mammary non-tumorigenic epithelial cells MCF10A remains to be studied. In the present study, we demonstrate that treatment of MDA-MB-231 cells for 48 h with 90 mM LA does not induce an increase in the number of secreted EVs. In addition, EVs isolated from supernatants of MDA-MB-231 stimulated for 48 h with 90 mM LA induce a transient down-regulation of E-cadherin expression, and an increase of Snail1 and 2, Twist1 and 2, Sip1, vimentin and N-cadherin expression in MCF10A cells. EVs also promote an increase of MMP-2 and -9 secretions, an increase of NFκB-DNA binding activity, migration and invasion in MCF10A cells. In summary, our findings demonstrate, for the first time, that EVs isolated from supernatants of MDA-MB-231 stimulated for 48 h with 90 mM LA induce an EMT-like process in MCF10A cells. 2014 Published by Elsevier Ltd
Medical oncology (Northwood, London, England), 2017
An increased risk of developing breast cancer has been associated with high levels of dietary fat intake. Linoleic acid (LA) is an essential fatty acid and the major ω-6 polyunsaturated fatty acid in occidental diets, which is able to induce inappropriate inflammatory responses that contribute to several chronic diseases including cancer. In breast cancer cells, LA induces migration. However, the signal transduction pathways that mediate migration and whether LA induces invasion in MDA-MB-231 breast cancer cells have not been studied in detail. We demonstrate here that LA induces Akt2 activation, invasion, an increase in NFκB-DNA binding activity, miR34a upregulation and miR9 downregulation in MDA-MB-231 cells. Moreover, Akt2 activation requires EGFR and PI3K activity, whereas migration and invasion are dependent on FFAR4, EGFR and PI3K/Akt activity. Our findings demonstrate, for the first time, that LA induces migration and invasion through an EGFR-/PI3K-/Akt-dependent pathway in M...
Endocrine Connections, 2019
Free fatty acids (FFAs) are an energy source, and induce activation of signal transduction pathways that mediate several biological processes. In breast cancer cells, oleic acid (OA) induces proliferation, matrix metalloproteinase-9 (MMP-9) secretion, migration and invasion. However, the signal transduction pathways that mediate migration and invasion induced by OA in breast cancer cells have not been studied in detail. We demonstrate here that FFAR1 and FFAR4 mediate migration induced by OA in MDA-MB-231 and MCF-7 breast cancer cells. Moreover, OA induces migration, invasion, AKT1 and AKT2 activation, 12-LOX secretion and an increase of NFκB-DNA binding activity in breast cancer cells. Cell migration requires FFAR1, FFAR4, EGFR, AKT and PI3K activity, whereas invasion is mediated though a PI3K/Akt-dependent pathway. Furthermore, OA promotes relocalization of paxillin to focal contacts and it requires PI3K and EGFR activity, whereas NFκB-DNA binding activity requires PI3K and AKT ac...
Cellular Oncology, 2013
Background Epidemiological studies and animal models suggest a link between high levels of dietary fat intake and an increased risk of developing breast cancer. Particularly, free fatty acids (FFAs) are involved in several processes, including proliferation, migration and invasion, in breast cancer cells. Linoleic acid (LA) is a dietary n-6 polyunsaturated fatty acid that is known to induce proliferation and invasion in breast cancer cells. So far, however, the contribution of LA to focal adhesion kinase (FAK) activation and cell migration in breast cancer cells has not been studied. Results Here, we show that LA promotes FAK and Src activation, as well as cell migration, in MDA-MB-231 breast cancer cells. FAK activation and cell migration require Src, Gi/Go, COX-2 and LOXs activities, whereas both are independent of Δ6 desaturase activity. In addition, we show that cell migration requires FAK activity, whereas FAK activation requires Src activity, thus suggesting a reciprocal catalytic activation mechanism of FAK and Src. Conclusions In summary, our findings show that LA induces FAK activation and cell migration in MDA-MB-231 breast cancer cells.
Molecular and cellular biochemistry, 2017
Epidemiological studies strongly suggest an association between high levels of dietary fat intake and an increased risk of developing breast cancer. Linoleic acid (LA) is an essential omega-6 PUFA and the major fatty acid in occidental diets. In breast cancer cells, LA induces expression of plasminogen activator inhibitor-1, proliferation, migration, and invasion. Fascin is an actin crosslinker globular protein that generates actin bundles made of parallel actin filaments, which mediate formation and stability of microspikes, stress fibers, membrane ruffles, and filopodia. However, the role of fascin in migration and invasion induced by LA in MDA-MB-231 breast cancer cells remains to be studied. We demonstrate here that LA induces an increase of fascin expression in MDA-MB-231 and MCF12A mammary epithelial cells. Particularly, LA induces the formation of filopodia and lamellipodia and the localization of fascin in these actin structures in MDA-MB-231 breast cancer cells. However, LA...
Linoleic acid induces an EMT-like process in mammary epithelial cells MCF10A
International Journal of Biochemistry & Cell Biology, 2011
Epidemiological studies and animal models suggest an association between high levels of dietary fat intake and an increased risk of developing breast cancer. Epithelial–mesenchymal-transition (EMT) is a process, by which epithelial cells are transdifferentiated to a mesenchymal state, and it has been implicated in cancer progression, including invasion and metastasis. Linoleic acid (LA) induces proliferation and invasion in breast cancer
CLA reduces breast cancer cell growth and invasion through ERα and PI3K/Akt pathways
Chemico-Biological Interactions, 2010
Keywords: CLA MCF-7 MDA-MB-231 ER␣ PI3K/Akt -Catenin/E-cadherin a b s t r a c t We previously reported that conjugated linoleic acid (CLA), a naturally occurring fatty acid, inhibits the growth of ER␣(+) MCF-7 and ER␣(−) MDA-MB-231 human breast cancer cells by negative modulation of the ERK/MAPK pathway and apoptosis induction. Here we show that in these cell lines CLA also downregulates the PI3K/Akt cascade. In MCF-7 cells CLA also triggers ER␣/PP2A complex formation reducing the phosphorylation state and transcriptional activity of Er␣ whereas in MDA-MB-231 cells CLA does not induce PP2A activation.
CLA reduces breast cancer cell growth and invasion through ERa and PI3K/Akt pathways
Chem Biol Inter, 2010
Keywords: CLA MCF-7 MDA-MB-231 ER␣ PI3K/Akt -Catenin/E-cadherin a b s t r a c t We previously reported that conjugated linoleic acid (CLA), a naturally occurring fatty acid, inhibits the growth of ER␣(+) MCF-7 and ER␣(−) MDA-MB-231 human breast cancer cells by negative modulation of the ERK/MAPK pathway and apoptosis induction. Here we show that in these cell lines CLA also downregulates the PI3K/Akt cascade. In MCF-7 cells CLA also triggers ER␣/PP2A complex formation reducing the phosphorylation state and transcriptional activity of Er␣ whereas in MDA-MB-231 cells CLA does not induce PP2A activation.
Extracellular vesicles (EVs) mediate many stages of tumor progression including angiogenesis, escape from immune surveillance, and extracellular matrix degradation. We studied whether EVs from plasma of women with breast cancer are able to induce an epithelial-mesenchymal transition (EMT) process in mammary epithelial cells MCF10A. Our findings demonstrate that EVs from plasma of breast cancer patients induce a downregulation of E-cadherin expression and an increase of vimentin and N-cadherin expression. Moreover, EVs induce migration and invasion, as well as an increase of NFκB-DNA binding activity and MMP-2 and MMP-9 secretions. In summary, our findings demonstrate, for the first time, that EVs from breast cancer patients induce an EMT-like process in human mammary non-tumorigenic epithelial cells MCF10A