Impact of flavonoids on matrix metalloproteinase secretion and invadopodia formation in highly invasive A431-III cancer cells.
Metastasis is a major cause of mortality in cancer patients. Invadopodia are considered to be crucial structures that allow cancer cells to penetrate across the extracellular matrix (ECM) by using matrix metalloproteinases (MMPs). Previously, we isolated a highly invasive A431-III subline from paren...
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doaj-052f3cfa4a104b9a9eabb995c7fa93bd2020-11-25T02:16:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7190310.1371/journal.pone.0071903Impact of flavonoids on matrix metalloproteinase secretion and invadopodia formation in highly invasive A431-III cancer cells.Yo-Chuen LinPei-Hsun TsaiChun-Yu LinChia-Hsiung ChengTsung-Han LinKevin P H LeeKai-Yun HuangShih-Hsun ChenJiuan-Jiuan HwangChithan C KandaswamiMing-Ting LeeMetastasis is a major cause of mortality in cancer patients. Invadopodia are considered to be crucial structures that allow cancer cells to penetrate across the extracellular matrix (ECM) by using matrix metalloproteinases (MMPs). Previously, we isolated a highly invasive A431-III subline from parental A431 cells by Boyden chamber assay. The A431-III cells possess higher invasive and migratory abilities, elevated levels of MMP-9 and an enhanced epithelial-mesenchymal transition (EMT) phenotype. In this study, we discovered that A431-III cells had an increased potential to form invadopodia and an improved capacity to degrade ECM compared with the original A431 cells. We also observed enhanced phosphorylation levels of cortactin and Src in A431-III cells; these phosphorylated proteins have been reported to be the main regulators of invadopodia formation. Flavonoids, almost ubiquitously distributed in food plants and plant food products, have been documented to exhibit anti-tumor properties. Therefore, it was of much interest to explore the effects of flavonoid antioxidants on the metastatic activity of A431-III cells. Exposure of A431-III cells to two potent dietary flavonoids, namely luteolin (Lu) and quercetin (Qu), caused inhibition of invadopodia formation and decrement in ECM degradation. We conclude that Lu and Qu attenuate the phosphorylation of cortactin and Src in A431-III cells. As a consequence, there ensues a disruption of invadopodia generation and the suppression of MMP secretion. These changes, in concert, bring about a reduction in metastasis.http://europepmc.org/articles/PMC3749203?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yo-Chuen Lin Pei-Hsun Tsai Chun-Yu Lin Chia-Hsiung Cheng Tsung-Han Lin Kevin P H Lee Kai-Yun Huang Shih-Hsun Chen Jiuan-Jiuan Hwang Chithan C Kandaswami Ming-Ting Lee |
spellingShingle |
Yo-Chuen Lin Pei-Hsun Tsai Chun-Yu Lin Chia-Hsiung Cheng Tsung-Han Lin Kevin P H Lee Kai-Yun Huang Shih-Hsun Chen Jiuan-Jiuan Hwang Chithan C Kandaswami Ming-Ting Lee Impact of flavonoids on matrix metalloproteinase secretion and invadopodia formation in highly invasive A431-III cancer cells. PLoS ONE |
author_facet |
Yo-Chuen Lin Pei-Hsun Tsai Chun-Yu Lin Chia-Hsiung Cheng Tsung-Han Lin Kevin P H Lee Kai-Yun Huang Shih-Hsun Chen Jiuan-Jiuan Hwang Chithan C Kandaswami Ming-Ting Lee |
author_sort |
Yo-Chuen Lin |
title |
Impact of flavonoids on matrix metalloproteinase secretion and invadopodia formation in highly invasive A431-III cancer cells. |
title_short |
Impact of flavonoids on matrix metalloproteinase secretion and invadopodia formation in highly invasive A431-III cancer cells. |
title_full |
Impact of flavonoids on matrix metalloproteinase secretion and invadopodia formation in highly invasive A431-III cancer cells. |
title_fullStr |
Impact of flavonoids on matrix metalloproteinase secretion and invadopodia formation in highly invasive A431-III cancer cells. |
title_full_unstemmed |
Impact of flavonoids on matrix metalloproteinase secretion and invadopodia formation in highly invasive A431-III cancer cells. |
title_sort |
impact of flavonoids on matrix metalloproteinase secretion and invadopodia formation in highly invasive a431-iii cancer cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Metastasis is a major cause of mortality in cancer patients. Invadopodia are considered to be crucial structures that allow cancer cells to penetrate across the extracellular matrix (ECM) by using matrix metalloproteinases (MMPs). Previously, we isolated a highly invasive A431-III subline from parental A431 cells by Boyden chamber assay. The A431-III cells possess higher invasive and migratory abilities, elevated levels of MMP-9 and an enhanced epithelial-mesenchymal transition (EMT) phenotype. In this study, we discovered that A431-III cells had an increased potential to form invadopodia and an improved capacity to degrade ECM compared with the original A431 cells. We also observed enhanced phosphorylation levels of cortactin and Src in A431-III cells; these phosphorylated proteins have been reported to be the main regulators of invadopodia formation. Flavonoids, almost ubiquitously distributed in food plants and plant food products, have been documented to exhibit anti-tumor properties. Therefore, it was of much interest to explore the effects of flavonoid antioxidants on the metastatic activity of A431-III cells. Exposure of A431-III cells to two potent dietary flavonoids, namely luteolin (Lu) and quercetin (Qu), caused inhibition of invadopodia formation and decrement in ECM degradation. We conclude that Lu and Qu attenuate the phosphorylation of cortactin and Src in A431-III cells. As a consequence, there ensues a disruption of invadopodia generation and the suppression of MMP secretion. These changes, in concert, bring about a reduction in metastasis. |
url |
http://europepmc.org/articles/PMC3749203?pdf=render |
work_keys_str_mv |
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