title: ADP-ribosylation factor 1 (ARF1) takes part in cell proliferation and cell adhesion-mediated drug resistance (CAM-DR).
abstract: Cell adhesion-mediated drug resistance (CAM-DR) remains the primary obstacle in human multiple myeloma (MM) therapy. In this study, we aimed at investigating the expression and biologic function of ARF1 in MM. We determined that ARF1 expression was positively correlated with cell proliferation and knockdown of ARF1 contributed to CAM-DR. The enhancement in the adhesion of MM cells to fibronectin (FN) or the bone marrow stroma cell line HS-5 cells translated to an increased CAM-DR phenotype. Importantly, we showed that this CAM-DR phenotype was correlated with the phosphorylation of Akt and ERK in MM cells. Moreover, we sought to determine whether ARF1 could interact with p27 in RPMI8226 cells. Knockdown of ARF1 also significantly decreased pT157-p27 protein expression in RPMI8226 cells. Our research shows ARF1 may reverse CAM-DR by regulating phosphorylation of p27 at T157 in MM. Taken together, our data shed new light on the molecular mechanism of CAM-DR in MM, and targeting ARF1 may be a novel therapeutic approach for improving the effectiveness of chemotherapy in MM.
authors.affiliation: Department of Oncology, Affiliated Cancer Hospital of Nantong University, Nantong, Jiangsu, People's Republic of China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Xu
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Qiru
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: He
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Ding
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhong
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Yangyu
authors.initials: Y
authors.lastname: Ou
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Yaodong
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Hematology, Affiliated Hospital of Nantong University, Nantong University, Nantong, 22600, Jiangsu Province, People's Republic of China. hongliu63@163.com.|Department of Hematology, Affiliated Hospital of Nantong University, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226361, China. hongliu63@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, 30 North Tongyang Road, Pingchao, Nantong, 226361, Jiangsu, People's Republic of China. ntzlyyhesong515@ntu.edu.cn.
authors.forename: Song
authors.initials: S
authors.lastname: He
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers; D002448:Cell Adhesion / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D010766:Phosphorylation; D016016:Proportional Hazards Models; D034622:RNA Interference; D015398:Signal Transduction; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D050760:Cyclin-Dependent Kinase Inhibitor p27; D020823:ADP-Ribosylation Factor 1
keywords: ARF1; CAM-DR; Multiple myeloma; Proliferation; p27