Abstract
Benzo(a)pyrene (BaP) is one of the strongest carcinogens in cigarette smoke, which is an established human carcinogen. Twist, a transcription factor of the basic helix–loop–helix class, is reported to regulate lung cancer metastasis. Evidence has shown that BaP could induce Twist mRNA expression in non-small cell lung cancer (NSCLC) cell line A549 and promote lung adenocarcinoma cell invasion. However, it is unclear whether BaP promotes the migration and invasion of NSCLC cells by Twist modulation. A549 cell was exposed to BaP for different time. MTT assay was applied to assess cell proliferation. Silencing of Twist was done by small interfering RNA. Wound-healing assay was used to evaluate the capability of cell migration. Transwell assay was used to detect the capability of cell invasion. Western blotting and quantitative polymerase chain reaction were used to detect Twist expression. The levels of Twist protein expression and mRNA expression were increased with the treatment of BaP, compared with solvent control. The capability of wound healing of A549 cells was increased in BaP-treated group, compared with solvent control. BaP enhanced the capability of invasion of A549 cells. Twist knockdown could block the migration and invasion of A549 cells induced by BaP treatment. The mRNA levels of Twist were higher in metastatic NSCLC tissue samples than in primary NSCLC tissue samples, and higher levels of Twist mRNA were observed in metastatic NSCLC tissue samples with smoking history than in those with nonsmoking history. BaP treatment could promote the migration and invasion of NSCLC cells by up-regulating Twist expression.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Agova S, Groseva D, Panev T, Popov T, Toncheva D, Hadjidekova V (2005) Effect of environmental exposure to PAHs on somatic chromosomes. Turk J Med Sci 35:143–148
Davis R, Rizwani W, Banerjee S, Kovacs M, Haura E, Coppola D, Chellappan S (2009) Nicotine promotes tumor growth and metastasis in mouse models of lung cancer. PLoS ONE 4:e7524
Gopalakrishna R, Chen ZH, Gundimeda U (1994) Tobacco smoke tumor promoters, catechol and hydroquinone, induce oxidative regulation of protein kinase C and influence invasion and metastasis of lung carcinoma cells. Proc Natl Acad Sci USA 91:12233–12237
Hecht SS (2012) Lung carcinogenesis by tobacco smoke. Int J Cancer 131:2724–2732
Hui L, Zhang S, Dong X, Tian D, Cui Z, Qiu X (2013) Prognostic significance of twist and N-cadherin expression in NSCLC. PLoS ONE 8:e62171
Iizasa T, Momiki S, Bauer B, Caamano J, Metcalf R, Lechner J, Harris CC, Klein-Szanto AJ (1993) Invasive tumors derived from xenotransplanted, immortalized human cells after in vivo exposure to chemical carcinogens. Carcinogenesis 14:1789–1794
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90
Leng S, Dai Y, Niu Y, Pan Z, Li X, Cheng J, He F, Zheng Y (2004) Effects of genetic polymorphisms of metabolic enzymes on cytokinesis-block micronucleus in peripheral blood lymphocyte among coke-oven workers. Cancer Epidemiol Biomarkers Prev 13:1631–1639
Melchiori A, Colacci A, Lollini PL, De Giovanni C, Carlone S, Grilli S, Parodi S, Albini A (1992) Induction of invasive and experimental metastasis potential in BALB/c 3T3 cells by benzo(a)pyrene transformation. Invasion Metastasis 12:1–11
Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA (2008) Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 83:584–594
Nakashima H, Hashimoto N, Aoyama D, Kohnoh T, Sakamoto K, Kusunose M, Imaizumi K, Takeyama Y, Sato M, Kawabe T, Hasegawa Y (2012) Involvement of the transcription factor twist in phenotype alteration through epithelial-mesenchymal transition in lung cancer cells. Mol Carcinog 51:400–410
Qin Q, Xu Y, He T, Qin C, Xu J (2012) Normal and disease-related biological functions of Twist1 and underlying molecular mechanisms. Cell Res 22:90–106
Tammemagi CM, Neslund-Dudas C, Simoff M, Kvale P (2004) Smoking and lung cancer survival: the role of comorbidity and treatment. Chest 125:27–37
Ueng TH, Chang YL, Tsai YY, Su JL, Chan PK, Shih JY, Lee YC, Ma YC, Kuo ML (2010) Potential roles of fibroblast growth factor-9 in the benzo(a)pyrene-induced invasion in vitro and the metastasis of human lung adenocarcinoma. Arch Toxicol 84:651–660
Wang G, Dong W, Shen H, Mu X, Li Z, Lin X, Liu Y, Du J (2011) A comparison of Twist and E-cadherin protein expression in primary non-small-cell lung carcinoma and corresponding metastases. Eur J Cardiothorac Surg 39:1028–1032
Xu L, Deng X (2004) Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induces phosphorylation of mu- and m-calpain in association with increased secretion, cell migration, and invasion. J Biol Chem 279:53683–53690
Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117:927–939
Yang J, Mani SA, Weinberg RA (2006) Exploring a new twist on tumor metastasis. Cancer Res 66:4549–4552
Yoshino I, Kawano D, Oba T, Yamazaki K, Kometani T, Maehara Y (2006) Smoking status as a prognostic factor in patients with stage I pulmonary adenocarcinoma. Ann Thorac Surg 81:1189–1193
Yoshino I, Kometani T, Shoji F, Osoegawa A, Ohba T, Kouso H, Takenaka T, Yohena T, Maehara Y (2007) Induction of epithelial-mesenchymal transition-related genes by benzo[a]pyrene in lung cancer cells. Cancer 110:369–374
Acknowledgments
We would like to thank Isioma Enwerem’s kindly helps for editing the English language of this manuscript. This work was supported by the National Natural Science Foundation of China (U1204815).
Conflict of interest
All authors declare that there is no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
Yadong Wang and Wenlong Zhai have contributed equally to this work.
Rights and permissions
About this article
Cite this article
Wang, Y., Zhai, W., Wang, H. et al. Benzo(a)pyrene promotes A549 cell migration and invasion through up-regulating Twist. Arch Toxicol 89, 451–458 (2015). https://doi.org/10.1007/s00204-014-1269-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00204-014-1269-8