Tumor Biology

, Volume 37, Issue 7, pp 9979–9987 | Cite as

Twist may be associated with invasion and metastasis of hypoxic NSCLC cells

  • Ling Wei
  • Ju-Jie Sun
  • Yong-Chun Cui
  • Shu-Li Jiang
  • Xing-Wu Wang
  • Li-Yan Lv
  • Li Xie
  • Xian-Rang Song
Original Article


Hypoxia promotes tumor invasion and metastasis via multiple mechanisms, including epithelial-mesenchymal transition (EMT). Twist, an EMT regulator, has been disclosed to associate with invasion and metastasis as well as poor prognosis of many malignancies. However, it remains undefined whether Twist is involved in invasion and metastasis of hypoxic non-small cell lung cancer (NSCLC). In this study, protein levels of Twist, hypoxia-inducible factor-1α (HIF-1α), and EMT markers (E-cadherin and vimentin) were examined by immunohistochemistry in 76 lung cancer tissues from NSCLC patients. Expression of Twist and its correlation with HIF-1α, E-cadherin, and vimentin were analyzed. Small interfering RNA (siRNA) against Twist was used to knockdown Twist expression in hypoxic NSCLC cells, A549 and NCI-H460. Cellular invasion and protein levels of Twist, E-cadherin, and vimentin were evaluated by matrigel invasion assay and Western blot, respectively. Our results showed that in clinical samples, there was a significant association between Twist expression and differentiation degree, lymph node metastasis, and TNM stage. Correlation analysis demonstrated that expression of Twist was negatively correlated with E-cadherin expression, but positively associated with HIF-1α and vimentin expression. In cultured NSCLC cells, Twist messenger RNA (mRNA) and protein levels were upregulated under hypoxia, while knockdown of Twist suppressed potentiated invasion and expression of mesenchymal marker vimentin induced by hypoxia. Protein level of increased epithelial marker E-cadherin was shown along with Twist downregulation. These findings suggest that Twist promoting hypoxic invasion and metastasis of NSCLC may be associated with altered expression of EMT markers. Inhibition of Twist may be of therapeutic significance.


Twist Non-small cell lung cancer Hypoxia Invasion Metastasis Epithelial-mesenchymal transition 



This work was supported by grants from Shandong Province Science Foundation (ZR2010HM083, ZR2009CM141) and Shandong Health Department (2011HZ095, 2015WS0155).

Compliance with ethical standard

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Ling Wei
    • 1
  • Ju-Jie Sun
    • 2
  • Yong-Chun Cui
    • 3
  • Shu-Li Jiang
    • 4
  • Xing-Wu Wang
    • 1
  • Li-Yan Lv
    • 1
  • Li Xie
    • 1
  • Xian-Rang Song
    • 1
  1. 1.Shandong Provincial Key Laboratory of Radiation OncologyShandong Cancer Hospital and InstituteJinanChina
  2. 2.Department of PathologyShandong Cancer Hospital and InstituteJinanChina
  3. 3.Department of EducationShandong Cancer Hospital and InstituteJinanChina
  4. 4.Department of EndoscopyShandong Cancer Hospital and InstituteJinanChina

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