Nuclear shuttling of Y Box binding protein-1, its clinical relevance in cancer and as a therapeutic target

Vinoth Prasanna Gunasekaran,Kumari Nishi,Ganeshan Mathan,Vilwanathan Ravikumar

doi:10.3329/bjp.v11i2.26759

Abstract

<p class="Abstract">Y-box binding protein 1 (YB-1) is an imperative biomarker for the clinical out-come of cancer patients. An overexpression of YB-1 in cancerous and adjoining tissues is an indication of aggressiveness and advanced stages. In normal resting cells, YB-1 is localized in cytoplasm while in stress conditions like cancer, nuclear shuttling of YB-1 takes place. In this review, the clinical importance of YB-1 in different cancers and the mechanism behind YB-1 nuclear shuttling have been discussed in detail. Targeted chemotherapies or molecularly targeted drugs of great importance can target and block specific molecules implicated in tumor growth and progression. YB-1 has been considered as a bonafide oncogene and accumulating evidences show the therapeutic importance of YB-1. Therapeutic strategies targeting YB-1 may improve the survival rate in cancer patients. This review extensively discusses the therapeutic importance of YB-1.</p><p> </p>

Highlights

Y-box binding proteins are the members of cold shock proteins large family conserved from prokaryotes to human (Hunt and Morimoto, 1985; Horwitz et al, 1994)
Screening of human placental cDNA library constructs led to the identification of dbpA and dbpB genes and the sequence analysis showed that dbpB is completely and dbpA is 46% identical to Y-box binding protein 1 (YB-1)
In addition to function as a transcription factor YB-1 activates gene expression of the EGFR, MMP-2 and of the receptor tyrosine kinase c-MET associated with tumor cell adhesion, invasion and metastasis (Davies and Dunn, 2011)

Summary

Introduction

Y-box binding proteins are the members of cold shock proteins large family conserved from prokaryotes to human (Hunt and Morimoto, 1985; Horwitz et al, 1994). For breast cancer, such studies have anticipated the association of YB-1 in epithelial cell transformation by AKT pathway (Sutherland et al, 2005) and role of YB-1 as a target for ERK down-stream kinases RSK1 and RSK2 (Astanehe et al, 2012). A recent study shows an association between elevated cytoplasmic expression of YB-1 with tumor aggressiveness and poorer patient survival in early stage breast cancer.

Results

Conclusion