MDA-9/Syntenin-Slug transcriptional complex promote epithelial-mesenchymal transition and invasion/metastasis in lung adenocarcinoma

Lu Kai Wang, Szu Hua Pan, Yih Leong Chang, Pei Fang Hung, Shih Han Kao, Wen Lung Wang, Ching Wen Lin, Shuenn Chen Yang, Chen Hsien Liang, Chen Tu Wu, Tzu Hung Hsiao, Tse-Ming Hong, Pan Chyr Yang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Melanoma differentiation-associated gene-9 (MDA-9)/Syntenin is a novel therapeutic target because it plays critical roles in cancer progression and exosome biogenesis. Here we show that Slug, a key epithelial-mesenchymal-transition (EMT) regulator, is a MDA-9/Syntenin downstream target. Mitogen EGF stimulation increases Slug expression and MDA-9/Syntenin nuclear translocation. MDA-9/Syntenin uses its PDZ1 domain to bind with Slug, and this interaction further leads to HDAC1 recruitment, up-regulation of Slug transcriptional repressor activity, enhanced Slug-mediated EMT, and promotion of cancer invasion and metastasis. The PDZ domains and nuclear localization of MDA-9/Syntenin are both required for promoting Slug-mediated cancer invasion. Clinically, patients with high MDA-9/Syntenin and high Slug expressions were associated with poor overall survival compared to those with low expression in lung adenocarcinomas. Our findings provide evidence that MDA-9/Syntenin acts as a pivotal adaptor of Slug and it transcriptionally enhances Slug-mediated EMT to promote cancer invasion and metastasis.

Original languageEnglish
Pages (from-to)386-401
Number of pages16
JournalOncotarget
Volume7
Issue number1
DOIs
Publication statusPublished - 2016 Jan 1

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Syntenins
Gastropoda
Epithelial-Mesenchymal Transition
Melanoma
Neoplasm Metastasis
Genes
Neoplasms
Exosomes
PDZ Domains
Adenocarcinoma of lung
Mitogens
Epidermal Growth Factor

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Wang, Lu Kai ; Pan, Szu Hua ; Chang, Yih Leong ; Hung, Pei Fang ; Kao, Shih Han ; Wang, Wen Lung ; Lin, Ching Wen ; Yang, Shuenn Chen ; Liang, Chen Hsien ; Wu, Chen Tu ; Hsiao, Tzu Hung ; Hong, Tse-Ming ; Yang, Pan Chyr. / MDA-9/Syntenin-Slug transcriptional complex promote epithelial-mesenchymal transition and invasion/metastasis in lung adenocarcinoma. In: Oncotarget. 2016 ; Vol. 7, No. 1. pp. 386-401.
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abstract = "Melanoma differentiation-associated gene-9 (MDA-9)/Syntenin is a novel therapeutic target because it plays critical roles in cancer progression and exosome biogenesis. Here we show that Slug, a key epithelial-mesenchymal-transition (EMT) regulator, is a MDA-9/Syntenin downstream target. Mitogen EGF stimulation increases Slug expression and MDA-9/Syntenin nuclear translocation. MDA-9/Syntenin uses its PDZ1 domain to bind with Slug, and this interaction further leads to HDAC1 recruitment, up-regulation of Slug transcriptional repressor activity, enhanced Slug-mediated EMT, and promotion of cancer invasion and metastasis. The PDZ domains and nuclear localization of MDA-9/Syntenin are both required for promoting Slug-mediated cancer invasion. Clinically, patients with high MDA-9/Syntenin and high Slug expressions were associated with poor overall survival compared to those with low expression in lung adenocarcinomas. Our findings provide evidence that MDA-9/Syntenin acts as a pivotal adaptor of Slug and it transcriptionally enhances Slug-mediated EMT to promote cancer invasion and metastasis.",
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Wang, LK, Pan, SH, Chang, YL, Hung, PF, Kao, SH, Wang, WL, Lin, CW, Yang, SC, Liang, CH, Wu, CT, Hsiao, TH, Hong, T-M & Yang, PC 2016, 'MDA-9/Syntenin-Slug transcriptional complex promote epithelial-mesenchymal transition and invasion/metastasis in lung adenocarcinoma', Oncotarget, vol. 7, no. 1, pp. 386-401. https://doi.org/10.18632/ONCOTARGET.6299

MDA-9/Syntenin-Slug transcriptional complex promote epithelial-mesenchymal transition and invasion/metastasis in lung adenocarcinoma. / Wang, Lu Kai; Pan, Szu Hua; Chang, Yih Leong; Hung, Pei Fang; Kao, Shih Han; Wang, Wen Lung; Lin, Ching Wen; Yang, Shuenn Chen; Liang, Chen Hsien; Wu, Chen Tu; Hsiao, Tzu Hung; Hong, Tse-Ming; Yang, Pan Chyr.

In: Oncotarget, Vol. 7, No. 1, 01.01.2016, p. 386-401.

Research output: Contribution to journalArticle

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T1 - MDA-9/Syntenin-Slug transcriptional complex promote epithelial-mesenchymal transition and invasion/metastasis in lung adenocarcinoma

AU - Wang, Lu Kai

AU - Pan, Szu Hua

AU - Chang, Yih Leong

AU - Hung, Pei Fang

AU - Kao, Shih Han

AU - Wang, Wen Lung

AU - Lin, Ching Wen

AU - Yang, Shuenn Chen

AU - Liang, Chen Hsien

AU - Wu, Chen Tu

AU - Hsiao, Tzu Hung

AU - Hong, Tse-Ming

AU - Yang, Pan Chyr

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Melanoma differentiation-associated gene-9 (MDA-9)/Syntenin is a novel therapeutic target because it plays critical roles in cancer progression and exosome biogenesis. Here we show that Slug, a key epithelial-mesenchymal-transition (EMT) regulator, is a MDA-9/Syntenin downstream target. Mitogen EGF stimulation increases Slug expression and MDA-9/Syntenin nuclear translocation. MDA-9/Syntenin uses its PDZ1 domain to bind with Slug, and this interaction further leads to HDAC1 recruitment, up-regulation of Slug transcriptional repressor activity, enhanced Slug-mediated EMT, and promotion of cancer invasion and metastasis. The PDZ domains and nuclear localization of MDA-9/Syntenin are both required for promoting Slug-mediated cancer invasion. Clinically, patients with high MDA-9/Syntenin and high Slug expressions were associated with poor overall survival compared to those with low expression in lung adenocarcinomas. Our findings provide evidence that MDA-9/Syntenin acts as a pivotal adaptor of Slug and it transcriptionally enhances Slug-mediated EMT to promote cancer invasion and metastasis.

AB - Melanoma differentiation-associated gene-9 (MDA-9)/Syntenin is a novel therapeutic target because it plays critical roles in cancer progression and exosome biogenesis. Here we show that Slug, a key epithelial-mesenchymal-transition (EMT) regulator, is a MDA-9/Syntenin downstream target. Mitogen EGF stimulation increases Slug expression and MDA-9/Syntenin nuclear translocation. MDA-9/Syntenin uses its PDZ1 domain to bind with Slug, and this interaction further leads to HDAC1 recruitment, up-regulation of Slug transcriptional repressor activity, enhanced Slug-mediated EMT, and promotion of cancer invasion and metastasis. The PDZ domains and nuclear localization of MDA-9/Syntenin are both required for promoting Slug-mediated cancer invasion. Clinically, patients with high MDA-9/Syntenin and high Slug expressions were associated with poor overall survival compared to those with low expression in lung adenocarcinomas. Our findings provide evidence that MDA-9/Syntenin acts as a pivotal adaptor of Slug and it transcriptionally enhances Slug-mediated EMT to promote cancer invasion and metastasis.

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