Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, China.
Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, China.
Biochem Biophys Res Commun. 2018 Jun 2;500(2):302-309. doi: 10.1016/j.bbrc.2018.04.064. Epub 2018 Apr 19.
Previously, BEX family members have been reported to participate in cancer development. However, little is known about the role of BEX4 in lung adenocarcinoma (LAC). Here, we found that BEX4 was over-expressed in LAC tissues compared with adjacent tissues. LAC tissues from metastatic patients exhibited higher expression of BEX4 comparing to those from non-metastatic ones. In vitro, BEX4 ectopic expression accelerated the proliferation of both A549 and H1975 cells. By contrast, knockdown of BEX4 suppressed the proliferation of A549 and H1975 cells. BEX4 positively regulated the expression of OCT4, silencing of which reduced the proliferation of A549 and H1975 cells with over-expressed BEX4. Additionally, mTOR activation, which is frequently observed in LAC, potentiated BEX4 depending on mTORC1 but not mTORC2. BEX4 abundance dictated the sensitivity of A549 and H1975 cells to rapamycin treatment. Our findings reveal that BEX4 is an oncogene in LAC and may contribute to the hyper-active mTOR-induced LAC development.
先前有报道称 BEX 家族成员参与癌症的发生发展。然而，BEX4 在肺腺癌（LAC）中的作用知之甚少。在这里，我们发现与相邻组织相比，BEX4 在 LAC 组织中表达上调。与非转移性 LAC 组织相比，转移性 LAC 组织中 BEX4 的表达更高。在体外，BEX4 的异位表达加速了 A549 和 H1975 细胞的增殖。相比之下，BEX4 的敲低抑制了 A549 和 H1975 细胞的增殖。BEX4 正向调控 OCT4 的表达，沉默 OCT4 可降低过表达 BEX4 的 A549 和 H1975 细胞的增殖。此外，LAC 中经常观察到的 mTOR 激活依赖于 mTORC1 而不是 mTORC2 增强 BEX4。BEX4 的丰度决定了 A549 和 H1975 细胞对雷帕霉素治疗的敏感性。我们的研究结果表明，BEX4 是 LAC 的致癌基因，可能有助于过度活跃的 mTOR 诱导的 LAC 发展。
