title: Y-box-binding protein-1 (YB-1) promotes cell proliferation, adhesion and drug resistance in diffuse large B-cell lymphoma.
abstract: YB-1 is a multifunctional protein, which has been shown to correlate with resistance to treatment of various tumor types. This study investigated the expression and biologic function of YB-1 in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical analysis showed that the expression statuses of YB-1 and pYB-1(S102) were reversely correlated with the clinical outcomes of DLBCL patients. In addition, we found that YB-1 could promote the proliferation of DLBCL cells by accelerating the G1/S transition. Ectopic expression of YB-1 could markedly increase the expression of cell cycle regulators cyclin D1 and cyclin E. Furthermore, we found that adhesion of DLBCL cells to fibronectin (FN) could increase YB-1 phosphorylation at Ser102 and pYB-1(S102) nuclear translocation. In addition, overexpression of YB-1 could increase the adhesion of DLBCL cells to FN. Intriguingly, we found that YB-1 overexpression could confer drug resistance through cell-adhesion dependent and independent mechanisms in DLBCL. Silencing of YB-1 could sensitize DLBCL cells to mitoxantrone and overcome cell adhesion-mediated drug resistance (CAM-DR) phenotype in an AKT-dependent manner.
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Miao
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu, China.
authors.forename: Yaxun
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pathogen, Medical College, Nantong University, Nantong 226001, Jiangsu, China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Yuchan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu, China.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu, China.
authors.forename: Haibing
authors.initials: H
authors.lastname: Yin
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu, China.
authors.forename: Chunsun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu, China.
authors.forename: Yushan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Shen
authors.affiliation: Department of Oncology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu, China. Electronic address: xuxiaohongnantong@126.com.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu, China. Electronic address: hesongnt@126.com.
authors.forename: Song
authors.initials: S
authors.lastname: He
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000494:pharmacology; D015999:Multivariate Analysis; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism*
chemical_list: D051840:Y-Box-Binding Protein 1; D010768:Phosphoserine; D008942:Mitoxantrone; D051057:Proto-Oncogene Proteins c-akt
keywords: Adhesion; Diffuse large B-cell lymphoma (DLBCL); Drug resistance; Proliferation; YB-1