University of Portsmouth, School of Pharmacy and Biomedical Sciences, White Swan Road, St. Michael's Building, PO1 2DT Portsmouth, United Kingdom; University of Hawaii Cancer Center, Cancer Biology Program, 701 Ilalo street, Honolulu, HI 96813, USA.
Exp Cell Res. 2019 Mar 15;376(2):221-226. doi: 10.1016/j.yexcr.2019.02.014. Epub 2019 Feb 16.
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.
在过去的十年中，越来越多的证据表明脑表达的 X 连锁 2（BEX2）在致癌过程中具有重要作用。综合现有研究表明，该基因在多种恶性肿瘤中具有致癌作用，包括乳腺癌、结直肠癌和肝细胞癌，以及脑肿瘤。BEX2 在乳腺癌中的鉴定源于基因表达微阵列研究。随后的研究表明，BEX2 通过调节线粒体凋亡途径和 G1 细胞周期促进乳腺癌细胞的生长和存活。在此过程中，BEX2 与 NF-κB、c-Jun/JNK 和 ErbB2 途径发生交叉对话。值得注意的是，几项研究发现 BEX2 在与乳腺癌观察到的类似信号功能相关的其他恶性肿瘤中具有致癌作用。在脑肿瘤中，BEX2 促进少突胶质细胞瘤和神经胶质瘤细胞的迁移和侵袭。此外，BEX2 表达通过 JNK 途径保护神经胶质瘤细胞免受凋亡，并通过 NF-κB p65 促进神经胶质瘤细胞增殖。此外，已经表明 BEX2 通过 JNK/c-Jun 途径促进细胞增殖，并调节结直肠癌中的 JNK/c-Jun 磷酸化。最近，已经证明 BEX2 表达是细胞增殖和乙型肝炎病毒介导的肝细胞癌发展所必需的。因此，BEX2 在多种恶性肿瘤中的致癌作用得到了可重复数据的支持，并且 NF-κB 和 JNK/c-Jun 途径在该过程中通常受 BEX2 调节。鉴于这些发现，针对 BEX2 可能是多种恶性肿瘤有吸引力的治疗策略。
