title: Immunoglobulin-like transcript 4 promotes tumor progression and metastasis and up-regulates VEGF-C expression via ERK signaling pathway in non-small cell lung cancer.
abstract: Immunoglobulin-like transcript (ILT) 4 has long been thought to be cell-surface molecule in certain immune cells and negatively regulates immune response. Recently, overexpression of ILT4 has been observed in a few cancers with unknown function. Here, we showed manipulation of ILT4 affected non-small cell lung cancer (NSCLC) cell proliferation, migration and invasion in vitro analyses. In vivo, ILT4 promoted the tumor growth and metastasis. Furthermore, the phosphorylation of extracellular regulated protein kinases (ERK1/2) was enhanced in ILT4 overexpressing NSCLC cells. ERK1/2 specific inhibitor U0126 suppressed the proliferation, migration and invasion of those cells. Stepwise investigations demonstrated that vascular endothelial growth factor C (VEGF-C) was the downstream effector of ILT4 and ERK1/2. Silence of VEGF-C attenuated the migration and invasion activity of ILT4 overexpressing cells. Moreover, Kaplan-Meier survival analysis indicated that NSCLC patients with ILT4 positive expression had a poor patient survival. ILT4 and VEGF-C expression had notable positive correlation in cancer cells, and their co-expression was significantly associated with adverse prognostic factors. Our findings suggest that ILT4 drives NSCLC development in part on activation of ERK signaling which in turn upregulates VEGF-C. ILT4 could be a novel cancer therapeutic target for NSCLC.
authors.affiliation: Department of Oncology, School of Medicine, Shandong University, Jinan, Shandong, P. R. China.|Department of Oncology, Jinan Central Hospital, Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, School of Medicine, Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Xiaosun
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Jinan Central Hospital, Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Shuwen
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong, P. R. China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Medical Imaging, Jinan Central Hospital, Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Zhaolong
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D018450:Disease Progression; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D011971:Receptors, Immunologic / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
chemical_list: C491341:LILRB2 protein, human; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: ERK1/2; ILT4; NSCLC; VEGF-C; tumor progression