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Down-Regulation of 3-Phosphoinositide–Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells
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| Zeitschriftentitel: | Molecular Cancer Research |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , |
| In: | Molecular Cancer Research, 7, 2009, 6, S. 944-954 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
|
| Schlagwörter: |
| author_facet |
Liu, Ying Wang, Jingna Wu, Min Wan, Wuzhou Sun, Ronghua Yang, De Sun, Xiangjun Ma, Dalong Ying, Guoguang Zhang, Ning Liu, Ying Wang, Jingna Wu, Min Wan, Wuzhou Sun, Ronghua Yang, De Sun, Xiangjun Ma, Dalong Ying, Guoguang Zhang, Ning |
|---|---|
| author |
Liu, Ying Wang, Jingna Wu, Min Wan, Wuzhou Sun, Ronghua Yang, De Sun, Xiangjun Ma, Dalong Ying, Guoguang Zhang, Ning |
| spellingShingle |
Liu, Ying Wang, Jingna Wu, Min Wan, Wuzhou Sun, Ronghua Yang, De Sun, Xiangjun Ma, Dalong Ying, Guoguang Zhang, Ning Molecular Cancer Research Down-Regulation of 3-Phosphoinositide–Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells Cancer Research Oncology Molecular Biology |
| author_sort |
liu, ying |
| spelling |
Liu, Ying Wang, Jingna Wu, Min Wan, Wuzhou Sun, Ronghua Yang, De Sun, Xiangjun Ma, Dalong Ying, Guoguang Zhang, Ning 1541-7786 1557-3125 American Association for Cancer Research (AACR) Cancer Research Oncology Molecular Biology http://dx.doi.org/10.1158/1541-7786.mcr-08-0368 <jats:title>Abstract</jats:title> <jats:p>High expression of 3-phosphoinositide–dependent protein kinase-1 (PDK1) has been detected in various invasive cancers. In the current study, we investigated its role in cancer cell migration and experimental metastasis. Down-regulation of PDK1 expression by small interference RNA markedly inhibited spontaneous migration and epidermal growth factor (EGF)–induced chemotaxis of human breast cancer cells. The defects were rescued by expressing wild-type PDK1. PDK1-depleted cells showed impaired EGF-induced actin polymerization and adhesion, probably due to a decrease in phosphorylation of LIM kinase/cofilin and integrin β1. Confocal microscopy revealed that EGF induced cotranslocation of PDK1 with Akt and protein kinase Cζ (PKCζ), regulators of LIM kinase, and integrin β1. Furthermore, PDK1 depletion dampened EGF-induced phosphorylation and translocation of Akt and PKCζ, suggesting that Akt and PKCζ functioned downstream of PDK1 in the chemotactic signaling pathway. In severe combined immunodeficiency mice, PDK1-depleted human breast cancer cells formed more slowly growing tumors and were defective in extravasation to mouse lungs after i.v. injection. Our results indicate that PDK1 plays an important role in regulating the malignant behavior of breast cancer cells, including their motility, through activation of Akt and PKCζ. Thus, PDK1, which increases its expression in cancer cells, can be used as a target for the development of novel therapies. (Mol Cancer Res 2009;7(6):944–54)</jats:p> Down-Regulation of 3-Phosphoinositide–Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells Molecular Cancer Research |
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| title |
Down-Regulation of 3-Phosphoinositide–Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells |
| title_unstemmed |
Down-Regulation of 3-Phosphoinositide–Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells |
| title_full |
Down-Regulation of 3-Phosphoinositide–Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells |
| title_fullStr |
Down-Regulation of 3-Phosphoinositide–Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells |
| title_full_unstemmed |
Down-Regulation of 3-Phosphoinositide–Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells |
| title_short |
Down-Regulation of 3-Phosphoinositide–Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells |
| title_sort |
down-regulation of 3-phosphoinositide–dependent protein kinase-1 levels inhibits migration and experimental metastasis of human breast cancer cells |
| topic |
Cancer Research Oncology Molecular Biology |
| url |
http://dx.doi.org/10.1158/1541-7786.mcr-08-0368 |
| publishDate |
2009 |
| physical |
944-954 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>High expression of 3-phosphoinositide–dependent protein kinase-1 (PDK1) has been detected in various invasive cancers. In the current study, we investigated its role in cancer cell migration and experimental metastasis. Down-regulation of PDK1 expression by small interference RNA markedly inhibited spontaneous migration and epidermal growth factor (EGF)–induced chemotaxis of human breast cancer cells. The defects were rescued by expressing wild-type PDK1. PDK1-depleted cells showed impaired EGF-induced actin polymerization and adhesion, probably due to a decrease in phosphorylation of LIM kinase/cofilin and integrin β1. Confocal microscopy revealed that EGF induced cotranslocation of PDK1 with Akt and protein kinase Cζ (PKCζ), regulators of LIM kinase, and integrin β1. Furthermore, PDK1 depletion dampened EGF-induced phosphorylation and translocation of Akt and PKCζ, suggesting that Akt and PKCζ functioned downstream of PDK1 in the chemotactic signaling pathway. In severe combined immunodeficiency mice, PDK1-depleted human breast cancer cells formed more slowly growing tumors and were defective in extravasation to mouse lungs after i.v. injection. Our results indicate that PDK1 plays an important role in regulating the malignant behavior of breast cancer cells, including their motility, through activation of Akt and PKCζ. Thus, PDK1, which increases its expression in cancer cells, can be used as a target for the development of novel therapies. (Mol Cancer Res 2009;7(6):944–54)</jats:p> |
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| author | Liu, Ying, Wang, Jingna, Wu, Min, Wan, Wuzhou, Sun, Ronghua, Yang, De, Sun, Xiangjun, Ma, Dalong, Ying, Guoguang, Zhang, Ning |
| author_facet | Liu, Ying, Wang, Jingna, Wu, Min, Wan, Wuzhou, Sun, Ronghua, Yang, De, Sun, Xiangjun, Ma, Dalong, Ying, Guoguang, Zhang, Ning, Liu, Ying, Wang, Jingna, Wu, Min, Wan, Wuzhou, Sun, Ronghua, Yang, De, Sun, Xiangjun, Ma, Dalong, Ying, Guoguang, Zhang, Ning |
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| description | <jats:title>Abstract</jats:title> <jats:p>High expression of 3-phosphoinositide–dependent protein kinase-1 (PDK1) has been detected in various invasive cancers. In the current study, we investigated its role in cancer cell migration and experimental metastasis. Down-regulation of PDK1 expression by small interference RNA markedly inhibited spontaneous migration and epidermal growth factor (EGF)–induced chemotaxis of human breast cancer cells. The defects were rescued by expressing wild-type PDK1. PDK1-depleted cells showed impaired EGF-induced actin polymerization and adhesion, probably due to a decrease in phosphorylation of LIM kinase/cofilin and integrin β1. Confocal microscopy revealed that EGF induced cotranslocation of PDK1 with Akt and protein kinase Cζ (PKCζ), regulators of LIM kinase, and integrin β1. Furthermore, PDK1 depletion dampened EGF-induced phosphorylation and translocation of Akt and PKCζ, suggesting that Akt and PKCζ functioned downstream of PDK1 in the chemotactic signaling pathway. In severe combined immunodeficiency mice, PDK1-depleted human breast cancer cells formed more slowly growing tumors and were defective in extravasation to mouse lungs after i.v. injection. Our results indicate that PDK1 plays an important role in regulating the malignant behavior of breast cancer cells, including their motility, through activation of Akt and PKCζ. Thus, PDK1, which increases its expression in cancer cells, can be used as a target for the development of novel therapies. (Mol Cancer Res 2009;7(6):944–54)</jats:p> |
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| imprint | American Association for Cancer Research (AACR), 2009 |
| imprint_str_mv | American Association for Cancer Research (AACR), 2009 |
| institution | DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14 |
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| spelling | Liu, Ying Wang, Jingna Wu, Min Wan, Wuzhou Sun, Ronghua Yang, De Sun, Xiangjun Ma, Dalong Ying, Guoguang Zhang, Ning 1541-7786 1557-3125 American Association for Cancer Research (AACR) Cancer Research Oncology Molecular Biology http://dx.doi.org/10.1158/1541-7786.mcr-08-0368 <jats:title>Abstract</jats:title> <jats:p>High expression of 3-phosphoinositide–dependent protein kinase-1 (PDK1) has been detected in various invasive cancers. In the current study, we investigated its role in cancer cell migration and experimental metastasis. Down-regulation of PDK1 expression by small interference RNA markedly inhibited spontaneous migration and epidermal growth factor (EGF)–induced chemotaxis of human breast cancer cells. The defects were rescued by expressing wild-type PDK1. PDK1-depleted cells showed impaired EGF-induced actin polymerization and adhesion, probably due to a decrease in phosphorylation of LIM kinase/cofilin and integrin β1. Confocal microscopy revealed that EGF induced cotranslocation of PDK1 with Akt and protein kinase Cζ (PKCζ), regulators of LIM kinase, and integrin β1. Furthermore, PDK1 depletion dampened EGF-induced phosphorylation and translocation of Akt and PKCζ, suggesting that Akt and PKCζ functioned downstream of PDK1 in the chemotactic signaling pathway. In severe combined immunodeficiency mice, PDK1-depleted human breast cancer cells formed more slowly growing tumors and were defective in extravasation to mouse lungs after i.v. injection. Our results indicate that PDK1 plays an important role in regulating the malignant behavior of breast cancer cells, including their motility, through activation of Akt and PKCζ. Thus, PDK1, which increases its expression in cancer cells, can be used as a target for the development of novel therapies. (Mol Cancer Res 2009;7(6):944–54)</jats:p> Down-Regulation of 3-Phosphoinositide–Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells Molecular Cancer Research |
| spellingShingle | Liu, Ying, Wang, Jingna, Wu, Min, Wan, Wuzhou, Sun, Ronghua, Yang, De, Sun, Xiangjun, Ma, Dalong, Ying, Guoguang, Zhang, Ning, Molecular Cancer Research, Down-Regulation of 3-Phosphoinositide–Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells, Cancer Research, Oncology, Molecular Biology |
| title | Down-Regulation of 3-Phosphoinositide–Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells |
| title_full | Down-Regulation of 3-Phosphoinositide–Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells |
| title_fullStr | Down-Regulation of 3-Phosphoinositide–Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells |
| title_full_unstemmed | Down-Regulation of 3-Phosphoinositide–Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells |
| title_short | Down-Regulation of 3-Phosphoinositide–Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells |
| title_sort | down-regulation of 3-phosphoinositide–dependent protein kinase-1 levels inhibits migration and experimental metastasis of human breast cancer cells |
| title_unstemmed | Down-Regulation of 3-Phosphoinositide–Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells |
| topic | Cancer Research, Oncology, Molecular Biology |
| url | http://dx.doi.org/10.1158/1541-7786.mcr-08-0368 |