title: Twist may be associated with invasion and metastasis of hypoxic NSCLC cells.
abstract: 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.
authors.affiliation: Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, 440 Jiyan Road, Jinan, 250117, Shandong Province, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Pathology, Shandong Cancer Hospital and Institute, 440 Jiyan Road, Jinan, 250117, Shandong Province, China.
authors.forename: Ju-Jie
authors.initials: JJ
authors.lastname: Sun
authors.affiliation: Department of Education, Shandong Cancer Hospital and Institute, 440 Jiyan Road, Jinan, 250117, Shandong Province, China.
authors.forename: Yong-Chun
authors.initials: YC
authors.lastname: Cui
authors.affiliation: Department of Endoscopy, Shandong Cancer Hospital and Institute, 440 Jiyan Road, Jinan, 250117, Shandong Province, China.
authors.forename: Shu-Li
authors.initials: SL
authors.lastname: Jiang
authors.affiliation: Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, 440 Jiyan Road, Jinan, 250117, Shandong Province, China.
authors.forename: Xing-Wu
authors.initials: XW
authors.lastname: Wang
authors.affiliation: Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, 440 Jiyan Road, Jinan, 250117, Shandong Province, China.
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Lv
authors.affiliation: Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, 440 Jiyan Road, Jinan, 250117, Shandong Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.affiliation: Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, 440 Jiyan Road, Jinan, 250117, Shandong Province, China. songxianrang2013@163.com.
authors.forename: Xian-Rang
authors.initials: XR
authors.lastname: Song
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D051879:Twist-Related Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D014746:Vimentin
keywords: Epithelial-mesenchymal transition; Hypoxia; Invasion; Metastasis; Non-small cell lung cancer; Twist
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