title: ARMC8α promotes proliferation and invasion of non-small cell lung cancer cells by activating the canonical Wnt signaling pathway.
abstract: ARMC8 proteins are novel armadillo repeat containing proteins, which are well conserved in eukaryotes and are involved in a variety of processes such as cell migration, proliferation, tissue maintenance, signal transduction, and tumorigenesis. Armadillo repeat proteins include well-known proteins such as β-catenin and p120ctn. Our current knowledge of ARMC8, especially its role in cancer, is limited. In this study, we quantified ARMC8 expression in 112 non-small cell lung cancer (NSCLC) tissues and adjacent non-cancerous tissues, and seven lung cancer cell lines using immunohistochemistry staining and Western blotting. ARMC8 level was significantly higher in NSCLC tissues than in the adjacent normal tissues (67.9 % versus 5.4 %, p < 0.05) and was significantly associated with TNM stage (p = 0.022), lymph node metastasis (p = 0.001), and poor prognosis (p < 0.001) in NSCLC patients. Cox regression analysis demonstrated that ARMC8 was an independent prognostic factor for NSCLC. Consistent with this, ARMC8α downregulation by siRNA knockdown inhibited growth, colony formation, and invasion in A549 lung cancer cells, while ARMC8α overexpression promoted growth, colony formation, and invasion in H1299 lung cancer cells. In addition, ARMC8α knockdown downregulated canonical Wnt-signaling pathway activity and cyclin D1 and matrix metalloproteinase (MMP)-7 expression. Consistent with this, ARMC8α overexpression upregulated canonical Wnt-signaling pathway activity and cyclin D1 and MMP-7 expression. These results indicate that ARMC8α upregulates cyclin D1 and MMP7 expression by activating the canonical Wnt-signaling pathway and thereby promoting lung cancer cell proliferation and invasion. Therefore, ARMC8 might serve as a novel therapeutic target in NSCLC.
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors.forename: Chengyao
authors.initials: C
authors.lastname: Xie
authors.forename: Guiyang
authors.initials: G
authors.lastname: Jiang
authors.forename: Chuifeng
authors.initials: C
authors.lastname: Fan
authors.forename: Xiupeng
authors.initials: X
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Miao
authors.forename: Xuyong
authors.initials: X
authors.lastname: Lin
authors.forename: Junhua
authors.initials: J
authors.lastname: Wu
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Juanhan
authors.initials: J
authors.lastname: Yu
authors.forename: Lianhe
authors.initials: L
authors.lastname: Yang
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051186:Armadillo Domain Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008207:Lymphatic Metastasis; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D011379:Prognosis; D016016:Proportional Hazards Models; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060449:Wnt Signaling Pathway
chemical_list: C522393:ARMC8 protein, human; D051186:Armadillo Domain Proteins; D019938:Cyclin D1; D020783:Matrix Metalloproteinase 7