Y-box binding protein-1 (YB-1) promotes cell cycle progression through CDC6-dependent pathway in human cancer cells

Abstract

Y-box binding protein-1 (YB-1) plays pivotal roles in acquisition of global drug resistance and cell growth promotion through transcriptional activation of genes for both drug resistance and growth factor receptors. In this study, we investigated whether YB-1 is involved in regulation of the cell cycle and cell proliferation of human cancer cells. Treatment with YB-1 siRNA caused a marked suppression of cell proliferation and expression of a cell cycle related gene, CDC6 by cancer cells. Of cell cycle of cancer cells, S phase content was specifically reduced by knockdown of YB-1. The overexpression of CDC6 abrogated this inhibition of both cell proliferation and S phase entry. ChIP assay demonstrated that YB-1 binds to a Y-box located in the promoter region of the CDC6 gene. Expression of cyclin D1, CDK1 and CDK2 was also reduced with increased expression of p21(Cip1) and p16(INK4A) when treated with YB-1 siRNA. Furthermore, the nuclear YB-1 expression was significantly associated with the level of CDC6 nuclear expression in patients with breast cancer. In conclusion, YB-1 plays an important role in cell cycle progression at G1/S of human cancer cells. YB-1 thus could be a potent biomarker for tumour growth and cell cycle in its close association with CDC6.

Y-box Binding Protein-1 Contributes to Both HER2/ErbB2 Expression and Lapatinib Sensitivity in Human Gastric Cancer Cells

“…We classified gastric cancer samples into high (2þ, 3þ) and low (0, 1þ) expression of EGFR, HER2, HER3, and CDC6. Consistent with the association of YB-1 with CDC6 in patients with breast cancer (25), nuclear YB-1 expression was found to be significantly associated with CDC6 expression (P < 0.0027) in gastric cancer in the present study (Table 1). Of the 3 EGFR family proteins, HER2 expression was significantly (P ¼ 0.026) correlated with YB-1.…”

“…YB-1 knockdown inhibits the cell proliferation of human breast cancer and suppresses the expression of various cell-cycle/DNA replication-related genes including cell division control protein 6 homolog (CDC6; ref. [23][24][25]. Astanehe and colleagues showed that YB-1 activation mediated drug resistance to trastuzumab through the mitogen-activated protein kinase-interacting kinase in breast cancer cells, suggesting a critical role for YB-1 in the acquirement of drug resistance to trastuzumab (26).…”

Y‐box binding protein‐1 is a novel molecular target for tumor vessels

“…We have recently reported that YB-1 positively regulates CDC6 expression and promotes cell cycle progression in human cancer cell lines. (34) Although immunohistochemical analysis shows that YB-1 expression is mainly observed in the cytoplasm of tumor-associated endothelial cells, it is possible that cytoplasmic YB-1 may translocate into nuclei at a specific phase of cell cycle to promote growth in normal cells. Further studies are required to provide insight into YB-1 function in normal cells.…”

Association of genetic variants in the retinoblastoma binding protein 6 gene with the risk of glioma: a case-control study in a Chinese Han population

“…What's more, the human RBBP6 protein had ubiquitin ligase activity through its RING finger domain 4 and Yb-1, which has been reported to be a proliferation gene, at least in breast cancer cells. 1,23,27 It was also shown to be one of the RBBP6 targets for ubiquitination. 9 In addition, the function of RBBP6 in modulating cell proliferation and survival has also been reported in pancreatic cancer, 24 and Mbita et al found that RBBP6 facilitates the evasion of cell cycle control and apoptosis in breast cancer.…”