Molecular functions of brain expressed X-linked 2 (BEX2) in malignancies

Highlights: • BEX2 expression is upregulated in several cancer types. • BEX2 has a pro-oncogenic function in multiple malignancies. • BEX2 has crosstalk with the NF-κB and c-Jun/JNK pathways. • BEX2 promotes cell survival and growth in multiple malignancies. • BEX2 is a potential cancer therapeutic target. -- Abstract: Over the last decade there has been growing evidence that Brain Expressed X-Linked 2 (BEX2) has a significant role in the process of carcinogenesis. Collectively, available studies suggest a pro-oncogenic function for this gene in multiple malignancies, including breast, colorectal and hepatocellular cancers in addition to brain tumors. The identification of BEX2 in breast cancer resulted from gene expression microarray studies. Subsequent studies showed that BEX2 promotes breast cancer cell growth and survival by modulating the mitochondrial apoptotic pathway and G1 cell cycle. In this process, BEX2 has cross-talk with the NF-κB, c-Jun/JNK and ErbB2 pathways. Of note, several studies have found a pro-oncogenic function for BEX2 in other malignancies associated with a similar signaling function to that observed in breast cancer. In brain tumors, BEX2 promotes cell migration and invasion in oligodendroglioma and glioblastoma cells. In addition, BEX2 expression protects glioma cells against apoptosis mediated through the JNK pathway and is required for glioma cell proliferation through the NF-κB p65. Furthermore, it has been shown that BEX2 promotes cell proliferation through the JNK/c-Jun pathway and regulates JNK/c-Jun phosphorylation in colorectal cancer. Most recently, it has been demonstrated that BEX2 expression is required for cell proliferation and Hepatitis B Virus-mediated development of hepatocellular carcinoma. Therefore, a pro-oncogenic function for BEX2 is supported by reproducible data in multiple malignancies and the NF-κB and JNK/c-Jun pathways are commonly regulated by BEX2 in this process. In view of these findings, targeting BEX2 may provide an attractive therapeutic strategy in multiple malignancies.