The Role of YB1 in Renal Cell Carcinoma Cell Adhesion

Background: Y-box binding protein 1 (YB1) is a multifunctional protein involved in many processes related to cancer progression and metastasis. Methods: In this study, we constructed YB1 knockdown stable renal cell carcinoma (RCC) cell line 786-0. The gene expression profile of 786-0 was performed by DNA microarray analysis to identify genes that were regulated by YB1. Real-time PCR and western blotting were used to test the genes and proteins expression. Transforming growth factor-β (TGF-β) activity was detected by dual-luciferase reporter assay. Cell adhesion assay was used to determine RCC cell adhesion ability. Results: Pathway analysis revealed that YB1 knockdown influenced cell adhesion molecules (CAMs). We further verified four genes (CLDN4, NRXN3, ITGB8, and VCAN) related to CAMs by real-time PCR, and confirmed that YB1 regulated the expression of ITGB8 in RCC. Functional assays demonstrated that knockdown of YB1 significantly inhibited the cell adhesion of 786-0 cells in vitro. In addition, YB1 affected TGF-β activation. Conclusion: Our study demonstrated that YB1 modulated the adhesion ability of renal cell carcinoma cells by regulating ITGB8 and TGF-β.

[1]  N. Beauchemin,et al.  Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis , 2013, Cancer and Metastasis Reviews.

[2]  S. Dunn,et al.  Interplay between YB-1 and IL-6 promotes the metastatic phenotype in breast cancer cells , 2015, Oncotarget.

[3]  Jun Cui,et al.  YB-1 overexpression promotes a TGF-β1-induced epithelial-mesenchymal transition via Akt activation. , 2015, Biochemical and biophysical research communications.

[4]  T. Guo,et al.  Transcriptional activation of NANOG by YBX1 promotes lung cancer stem-like properties and metastasis. , 2017, Biochemical and biophysical research communications.

[5]  K. Aldape,et al.  αvβ8 integrin interacts with RhoGDI1 to regulate Rac1 and Cdc42 activation and drive glioblastoma cell invasion , 2013, Molecular biology of the cell.

[6]  Y. Oda,et al.  Potential Role for YB-1 in Castration-Resistant Prostate Cancer and Resistance to Enzalutamide Through the Androgen Receptor V7. , 2016, Journal of the National Cancer Institute.

[7]  B. Rini,et al.  Current Treatment Considerations in Metastatic Renal Cell Carcinoma , 2012, Current Treatment Options in Oncology.

[8]  A. Nowakowski,et al.  Cyclin A correlates with YB1, progression and resistance to chemotherapy in human epithelial ovarian cancer. , 2015, Anticancer research.

[9]  P. Sorensen,et al.  Translational Activation of HIF1α by YB-1 Promotes Sarcoma Metastasis. , 2015, Cancer cell.

[10]  P. Wolters,et al.  Transcription of the Transforming Growth Factor β Activating Integrin β8 Subunit Is Regulated by SP3, AP-1, and the p38 Pathway* , 2010, The Journal of Biological Chemistry.

[11]  C. Knabbe,et al.  Y-box Binding Protein-1 Enhances Oncogenic Transforming Growth Factor β Signaling in Breast Cancer Cells via Triggering Phospho-Activation of Smad2. , 2017, Anticancer research.

[12]  C. Sorenson,et al.  Mesangial cell integrin αvβ8 provides glomerular endothelial cell cytoprotection by sequestering TGF-β and regulating PECAM-1. , 2011, The American journal of pathology.

[13]  Yunde Liu,et al.  Overexpression of YB1 and EZH2 are associated with cancer metastasis and poor prognosis in renal cell carcinomas , 2015, Tumor Biology.

[14]  D. Mu,et al.  Integrin alpha(v)beta8-mediated activation of transforming growth factor-beta by perivascular astrocytes: an angiogenic control switch. , 2005, The American journal of pathology.

[15]  D. Lindgren,et al.  Effects of TGF-β signaling in clear cell renal cell carcinoma cells. , 2013, Biochemical and biophysical research communications.

[16]  V. Khoo,et al.  Radiotherapy for renal-cell carcinoma. , 2014, The Lancet. Oncology.

[17]  J. Schelling,et al.  Mesangial cell αvβ8-integrin regulates glomerular capillary integrity and repair. , 2014, American journal of physiology. Renal physiology.

[18]  Konstantin G. Chernov,et al.  The mRNA-binding Protein YB-1 (p50) Prevents Association of the Eukaryotic Initiation Factor eIF4G with mRNA and Inhibits Protein Synthesis at the Initiation Stage* , 2003, The Journal of Biological Chemistry.

[19]  Chawnshang Chang,et al.  C1QBP Regulates YBX1 to Suppress the Androgen Receptor (AR)-Enhanced RCC Cell Invasion , 2017, Neoplasia.

[20]  R. Jha,et al.  Integrin Beta 8 (ITGB8) Regulates Embryo Implantation Potentially via Controlling the Activity of TGF-B1 in Mice1 , 2015, Biology of reproduction.

[21]  M. Gleave,et al.  YB‐1 is upregulated during prostate cancer tumor progression and increases P‐glycoprotein activity , 2004, The Prostate.

[22]  Hongyun Li,et al.  YBX1 promotes tumor growth by elevating glycolysis in human bladder cancer , 2017, Oncotarget.

[23]  Yunlong Liu,et al.  Critical role of phosphorylation of serine 165 of YBX1 on the activation of NF-κB in colon cancer , 2015, Oncotarget.

[24]  M. Moyle,et al.  Cloning and expression of a divergent integrin subunit beta 8. , 1991, The Journal of biological chemistry.

[25]  T. Guo,et al.  High expression of Y-box-binding protein 1 correlates with poor prognosis and early recurrence in patients with small invasive lung adenocarcinoma , 2016, OncoTargets and therapy.

[26]  Jung-Hye Choi,et al.  Mutant p53 promotes ovarian cancer cell adhesion to mesothelial cells via integrin β4 and Akt signals , 2015, Scientific Reports.

[27]  Ming Xin,et al.  Role of the interaction between galectin-3 and cell adhesion molecules in cancer metastasis. , 2015, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[28]  P. Tamboli,et al.  Pathology and Chinese a Nti鄄 Cancer a Ssociation Diagnosis and Classification of Rcc , 2022 .

[29]  Yunlong Liu,et al.  Novel Serine 176 Phosphorylation of YBX1 Activates NF-κB in Colon Cancer* , 2017, The Journal of Biological Chemistry.

[30]  Ruibing Chen,et al.  C1QBP negatively regulates the activation of oncoprotein YBX1 in the renal cell carcinoma as revealed by interactomics analysis. , 2015, Journal of proteome research.

[31]  R. Mantovani,et al.  Targeting the Y/CCAAT box in cancer: YB-1 (YBX1) or NF-Y? , 2013, Cell Death and Differentiation.