Y-box-binding protein-1 (YB-1) promotes cell proliferation, adhesion and drug resistance in diffuse large B-cell lymphoma

• Published in: Experimental cell research 2016-08, Vol.346 (2), p.157-166
• Main Authors: Miao, Xiaobing, Wu, Yaxun, Wang, Yuchan, Zhu, Xinghua, Yin, Haibing, He, Yunhua, Li, Chunsun, Liu, Yushan, Lu, Xiaoyun, Chen, Yali, Shen, Rong, Xu, Xiaohong, He, Song
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ADHESION; Cell adhesion & migration; Cell Adhesion - drug effects; CELL CYCLE; Cell Cycle - drug effects; Cell growth; Cell Line, Tumor; CELL PROLIFERATION; Cell Proliferation - drug effects; COMPUTER-AIDED MANUFACTURING; Diffuse large B-cell lymphoma (DLBCL); Drug resistance; Drug Resistance, Neoplasm - drug effects; DRUGS; Female; Humans; Lymphoma; Lymphoma, Large B-Cell, Diffuse - pathology; LYMPHOMAS; Male; Middle Aged; Mitoxantrone - pharmacology; Multivariate Analysis; PATIENTS; PHENOTYPE; PHOSPHORYLATION; Phosphorylation - drug effects; Phosphoserine - metabolism; Prognosis; Proliferation; Protein expression; PROTEINS; Proto-Oncogene Proteins c-akt - metabolism; TRANSLOCATION; Y-Box-Binding Protein 1 - metabolism; YB-1
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2016.07.003

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-1S102 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-1S102 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. •The expression statuses of YB-1 and pYB-1S102 are reversely correlated with outcomes of DLBCL patients.•YB-1 promotes cell proliferation by accelerating G1/S transition in DLBCL.•YB-1 confers drug resistance to mitoxantrone in DLBCL.