Knockdown of ZEB1, a master epithelial-to-mesenchymal transition (EMT) gene, suppresses anchorage-independent cell growth of lung cancer cells

Yoshihiro Takeyama; Mitsuo Sato; Mihoko Horio; Tetsunari Hase; Kenya Yoshida; Toshihiko Yokoyama; Harunori Nakashima; Naozumi Hashimoto; Yoshitaka Sekido; Adi F. Gazdar; John D. Minna; Masashi Kondo; Yoshinori Hasegawa

doi:10.1016/j.canlet.2010.04.008

Knockdown of ZEB1, a master epithelial-to-mesenchymal transition (EMT) gene, suppresses anchorage-independent cell growth of lung cancer cells

Yoshihiro Takeyama, Mitsuo Sato, Mihoko Horio, Tetsunari Hase, Kenya Yoshida, Toshihiko Yokoyama, Harunori Nakashima, Naozumi Hashimoto, Yoshitaka Sekido, Adi F. Gazdar, John D. Minna, Masashi Kondo, Yoshinori Hasegawa

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131 Scopus citations

Abstract

We found that among four master epithelial-to-mesenchymal transition (EMT)-inducing genes (ZEB1, SIP1, Snail, and Slug) ZEB1expression was most significantly correlated with the mesenchymal phenotype (high Vimentin and low E-cadherin expression) in non-small cell lung cancer (NSCLC) cell lines and tumors. Furthermore, ZEB1 knockdown with RNA interference in three NSCLC cell lines with high ZEB1 expression suppressed to varying degrees mass culture growth and liquid colony formation but in all cases dramatically suppressed soft agar colony formation. In addition, ZEB1 knockdown induced apoptosis in one of the three lines, indicating that the growth inhibitory effects of ZEB1 knockdown occurs in part through the activation of the apoptosis pathway. These results suggest that inhibiting ZEB1 function may be an attractive target for NSCLC therapeutic development.

Original language	English (US)
Pages (from-to)	216-224
Number of pages	9
Journal	Cancer Letters
Volume	296
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2010.04.008
State	Published - Oct 2010

Keywords

Anchorage-independent growth
EMT
Epidermal growth factor receptor
Lung cancer
MicroRNA
RNA interference

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.canlet.2010.04.008

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Takeyama, Y., Sato, M., Horio, M., Hase, T., Yoshida, K., Yokoyama, T., Nakashima, H., Hashimoto, N., Sekido, Y., Gazdar, A. F., Minna, J. D., Kondo, M., & Hasegawa, Y. (2010). Knockdown of ZEB1, a master epithelial-to-mesenchymal transition (EMT) gene, suppresses anchorage-independent cell growth of lung cancer cells. Cancer Letters, 296(2), 216-224. https://doi.org/10.1016/j.canlet.2010.04.008

Takeyama, Y, Sato, M, Horio, M, Hase, T, Yoshida, K, Yokoyama, T, Nakashima, H, Hashimoto, N, Sekido, Y, Gazdar, AF, Minna, JD, Kondo, M & Hasegawa, Y 2010, 'Knockdown of ZEB1, a master epithelial-to-mesenchymal transition (EMT) gene, suppresses anchorage-independent cell growth of lung cancer cells', Cancer Letters, vol. 296, no. 2, pp. 216-224. https://doi.org/10.1016/j.canlet.2010.04.008

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title = "Knockdown of ZEB1, a master epithelial-to-mesenchymal transition (EMT) gene, suppresses anchorage-independent cell growth of lung cancer cells",

abstract = "We found that among four master epithelial-to-mesenchymal transition (EMT)-inducing genes (ZEB1, SIP1, Snail, and Slug) ZEB1expression was most significantly correlated with the mesenchymal phenotype (high Vimentin and low E-cadherin expression) in non-small cell lung cancer (NSCLC) cell lines and tumors. Furthermore, ZEB1 knockdown with RNA interference in three NSCLC cell lines with high ZEB1 expression suppressed to varying degrees mass culture growth and liquid colony formation but in all cases dramatically suppressed soft agar colony formation. In addition, ZEB1 knockdown induced apoptosis in one of the three lines, indicating that the growth inhibitory effects of ZEB1 knockdown occurs in part through the activation of the apoptosis pathway. These results suggest that inhibiting ZEB1 function may be an attractive target for NSCLC therapeutic development.",

keywords = "Anchorage-independent growth, EMT, Epidermal growth factor receptor, Lung cancer, MicroRNA, RNA interference",

author = "Yoshihiro Takeyama and Mitsuo Sato and Mihoko Horio and Tetsunari Hase and Kenya Yoshida and Toshihiko Yokoyama and Harunori Nakashima and Naozumi Hashimoto and Yoshitaka Sekido and Gazdar, {Adi F.} and Minna, {John D.} and Masashi Kondo and Yoshinori Hasegawa",

note = "Funding Information: This work was supported by Grant-in-Aid for Scientific Research (C) 20590919 (to M.S.), Grant-in-Aid for Scientific Research (C) 20590918 (to M.K), and Grant-in-Aid for Scientific Research (B) 21390257 (to Y.H.) from Japan Society for the Promotion of Science, Global COE program in Nagoya University Graduate School of Medicine funded by Japan{\textquoteright}s Ministry of Education, Culture, Sports, Science and Technology, NCI Special Program of Research Excellence in lung Cancer (SPORE P50CA70907), and DOD PROSPECT (to JDM and AFG). We thank Dr. David S. Shames for his helpful comments and discussion on this study.",

year = "2010",

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doi = "10.1016/j.canlet.2010.04.008",

language = "English (US)",

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pages = "216--224",

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T1 - Knockdown of ZEB1, a master epithelial-to-mesenchymal transition (EMT) gene, suppresses anchorage-independent cell growth of lung cancer cells

AU - Takeyama, Yoshihiro

AU - Sato, Mitsuo

AU - Horio, Mihoko

AU - Hase, Tetsunari

AU - Yoshida, Kenya

AU - Yokoyama, Toshihiko

AU - Nakashima, Harunori

AU - Hashimoto, Naozumi

AU - Sekido, Yoshitaka

AU - Gazdar, Adi F.

AU - Minna, John D.

AU - Kondo, Masashi

AU - Hasegawa, Yoshinori

N1 - Funding Information: This work was supported by Grant-in-Aid for Scientific Research (C) 20590919 (to M.S.), Grant-in-Aid for Scientific Research (C) 20590918 (to M.K), and Grant-in-Aid for Scientific Research (B) 21390257 (to Y.H.) from Japan Society for the Promotion of Science, Global COE program in Nagoya University Graduate School of Medicine funded by Japan’s Ministry of Education, Culture, Sports, Science and Technology, NCI Special Program of Research Excellence in lung Cancer (SPORE P50CA70907), and DOD PROSPECT (to JDM and AFG). We thank Dr. David S. Shames for his helpful comments and discussion on this study.

PY - 2010/10

Y1 - 2010/10

N2 - We found that among four master epithelial-to-mesenchymal transition (EMT)-inducing genes (ZEB1, SIP1, Snail, and Slug) ZEB1expression was most significantly correlated with the mesenchymal phenotype (high Vimentin and low E-cadherin expression) in non-small cell lung cancer (NSCLC) cell lines and tumors. Furthermore, ZEB1 knockdown with RNA interference in three NSCLC cell lines with high ZEB1 expression suppressed to varying degrees mass culture growth and liquid colony formation but in all cases dramatically suppressed soft agar colony formation. In addition, ZEB1 knockdown induced apoptosis in one of the three lines, indicating that the growth inhibitory effects of ZEB1 knockdown occurs in part through the activation of the apoptosis pathway. These results suggest that inhibiting ZEB1 function may be an attractive target for NSCLC therapeutic development.

AB - We found that among four master epithelial-to-mesenchymal transition (EMT)-inducing genes (ZEB1, SIP1, Snail, and Slug) ZEB1expression was most significantly correlated with the mesenchymal phenotype (high Vimentin and low E-cadherin expression) in non-small cell lung cancer (NSCLC) cell lines and tumors. Furthermore, ZEB1 knockdown with RNA interference in three NSCLC cell lines with high ZEB1 expression suppressed to varying degrees mass culture growth and liquid colony formation but in all cases dramatically suppressed soft agar colony formation. In addition, ZEB1 knockdown induced apoptosis in one of the three lines, indicating that the growth inhibitory effects of ZEB1 knockdown occurs in part through the activation of the apoptosis pathway. These results suggest that inhibiting ZEB1 function may be an attractive target for NSCLC therapeutic development.

KW - Anchorage-independent growth

KW - EMT

KW - Epidermal growth factor receptor

KW - Lung cancer

KW - MicroRNA

KW - RNA interference

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Knockdown of ZEB1, a master epithelial-to-mesenchymal transition (EMT) gene, suppresses anchorage-independent cell growth of lung cancer cells

Abstract

Keywords

ASJC Scopus subject areas

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