Why Be One Protein When You Can Affect Many? The Multiple Roles of YB-1 in Lung Cancer and Mesothelioma

Abstract

Lung cancers and malignant pleural mesothelioma (MPM) have some of the worst 5-year survival rates of all cancer types, primarily due to a lack of effective treatment options for most patients. Targeted therapies have shown some promise in thoracic cancers, although efficacy is limited only to patients harboring specific mutations or target expression. Although a number of actionable mutations have now been identified, a large population of thoracic cancer patients have no therapeutic options outside of first-line chemotherapy. It is therefore crucial to identify alternative targets that might lead to the development of new ways of treating patients diagnosed with these diseases. The multifunctional oncoprotein Y-box binding protein-1 (YB-1) could serve as one such target. Recent studies also link this protein to many inherent behaviors of thoracic cancer cells such as proliferation, invasion, metastasis and involvement in cancer stem-like cells. Here, we review the regulation of YB-1 at the transcriptional, translational, post-translational and sub-cellular levels in thoracic cancer and discuss its potential use as a biomarker and therapeutic target.

Y-Box Binding Protein 1 Expression in Trophoblast Cells Promotes Fetal and Placental Development

“…A myriad of functions have been attributed to YB-1. Among these, YB-1 plays a major role in cancer development and progression due to its ability to support the proliferation, invasion and metastasis of various tumor cells [ 12 , 25 , 26 , 27 ]. Moreover, this cold shock protein is also relevant for the regulation of inflammatory responses due to the transcriptional and translational regulation of inflammatory mediators [ 28 , 29 , 30 ].…”

Y-Box Binding Proteins in mRNP Assembly, Translation, and Stability Control

“…Since one review can hardly cover all the proven and alleged roles of YB proteins in a cell or the whole organism, here we focus on peculiar interactions of these proteins with RNAs and their involvement in RNA-dependent processes, such as mRNA packaging into mRNPs, mRNA translation, and mRNA stabilization. Other no less interesting activities of YB proteins are described in several comprehensive reviews [1,[6][7][8][9][10][11].…”

Critical Role for Cold Shock Protein YB-1 in Cytokinesis

“…Furthermore, YB-1 has also been implicated in regulating the proliferation of breast cancer, large B-cell lymphoma, lung adenocarcinoma, neuroblastoma, hepatocellular carcinoma, glioma, renal cell carcinoma and melanoma in vitro [ 4 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. YB-1 has been implicated in regulating many genes involved in proliferation [ 10 , 11 , 12 , 13 , 14 , 15 ] and survival, reviewed in [ 1 , 17 ], including the 70-gene breast cancer “signature” [ 18 ] and the E2F family gene cluster [ 4 ]. YB-1 has also been shown to disable the p53 pathway to allow continued cellular propagation despite genomic insult [ 19 ].…”