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

Research output: Contribution to journalArticle

100 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)216-224
Number of pages9
JournalCancer Letters
Volume296
Issue number2
DOIs
StatePublished - Oct 2010

Fingerprint

Epithelial-Mesenchymal Transition
Non-Small Cell Lung Carcinoma
Lung Neoplasms
Growth
Apoptosis
Genes
Gastropoda
Vimentin
Cadherins
RNA Interference
Tumor Cell Line
Agar
Phenotype
Cell Line
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Knockdown of ZEB1, a master epithelial-to-mesenchymal transition (EMT) gene, suppresses anchorage-independent cell growth of lung cancer cells. / Takeyama, Yoshihiro; Sato, Mitsuo; Horio, Mihoko; Hase, Tetsunari; Yoshida, Kenya; Yokoyama, Toshihiko; Nakashima, Harunori; Hashimoto, Naozumi; Sekido, Yoshitaka; Gazdar, Adi F.; Minna, John D.; Kondo, Masashi; Hasegawa, Yoshinori.

In: Cancer Letters, Vol. 296, No. 2, 10.2010, p. 216-224.

Research output: Contribution to journalArticle

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
Takeyama, Yoshihiro ; Sato, Mitsuo ; Horio, Mihoko ; Hase, Tetsunari ; Yoshida, Kenya ; Yokoyama, Toshihiko ; Nakashima, Harunori ; Hashimoto, Naozumi ; Sekido, Yoshitaka ; Gazdar, Adi F. ; Minna, John D. ; Kondo, Masashi ; Hasegawa, Yoshinori. / Knockdown of ZEB1, a master epithelial-to-mesenchymal transition (EMT) gene, suppresses anchorage-independent cell growth of lung cancer cells. In: Cancer Letters. 2010 ; Vol. 296, No. 2. pp. 216-224.
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