title: Suppression of lung cancer cell invasion by LKB1 is due to the downregulation of tissue factor and vascular endothelial growth factor, partly dependent on SP1.
abstract: LKB1 encodes a serine/threonine kinase generally inactivated in many human cancers, which mediates cancer cell proliferation, migration and differentiation. Recent studies indicated that LKB1 exhibits potent anti-metastatic activity. However, the underlying molecular mechanisms of this activity remain unclear. In this study, we re‑introduced LKB1 into A549 lung cancer cells that lack the LKB1 gene to investigate how LKB1 affects tumor invasiveness and metastasis. We demonstrated that overexpression of the LKB1 protein in lung cancer cells resulted in significant inhibition of invasion. Furthermore, transfected lung cancer cells with LKB1 suppressed tissue factor (TF) and vascular endothelial growth factor (VEGF) expression at both the mRNA and protein levels. Here, we provided evidence showing that downregulation of TF and VEGF by LKB1 is correlated well with the inhibition of cell invasion. Overexpression of the LKB1 protein in human lung cancer is significantly associated with a decrease in activity and expression of the transcription factor SP1. Constitutive activation of the transcription factor Sp1 plays a critical role in TF and VEGF overexpression. We conclude that suppression of lung cancer cell invasion by LKB1 through downregulation of TF and VEGF may partly depend on its inhibitory effect on the transcription factor Sp1. Collectively, our data provide a novel molecular mechanism for the antitumor activity of LKB1 and may help further improve its effectiveness in controlling lung cancer growth and invasion.
authors.affiliation: Department of Oncology, First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Urology, Second Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Zhao-Lun
authors.initials: ZL
authors.lastname: Li
authors.affiliation: Department of Oncology, First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Jiang
authors.affiliation: Department of Oncology, First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Guo
authors.affiliation: Department of Oncology, First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Meng-Jie
authors.initials: MJ
authors.lastname: Liu
authors.affiliation: Department of Oncology, First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Ke-Jun
authors.initials: KJ
authors.lastname: Nan
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013925:Thromboplastin; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases