BPTF promotes tumor growth and predicts poor prognosis in lung adenocarcinomas.
BPTF promotes tumor growth and predicts poor prognosis in lung adenocarcinomas.
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DOI：
10.18632/oncotarget.5302
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发表时间：
2015-10-20
期刊：
影响因子：
--
通讯作者：
Wu T
中科院分区：
文献类型：
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作者：
Dai M;Lu JJ;Guo W;Yu W;Wang Q;Tang R;Tang Z;Xiao Y;Li Z;Sun W;Sun X;Qin Y;Huang W;Deng WG;Wu T
BPTF 是 NURF 的一个亚基，众所周知参与真核细胞的发育，但对其在癌症，特别是非小细胞肺癌 (NSCLC) 中的作用知之甚少。在这里，我们发现 BPTF 在 NSCLC 细胞系和肺腺癌组织中特异性过表达。 siRNA 敲低 BPTF 显着抑制细胞增殖，诱导细胞凋亡并阻止细胞周期从 G1 期进展到 S 期。我们还发现BPTF敲低下调了磷酸化的Erk1/2、PI3K和Akt蛋白的表达，并诱导caspase-8、caspase-7和PARP蛋白的裂解，从而抑制MAPK和PI3K/AKT信号传导并激活细胞凋亡途径。 siRNA 敲低 BPTF 还上调细胞周期抑制剂，如 p21 和 p18，但抑制肺癌细胞中细胞周期蛋白 D、磷酸化 Rb 和磷酸化 cdc2 的表达。此外，BPTF 通过其特异性 shRNA 敲除可抑制 A549 细胞异种移植物中肺癌的体内生长，同时抑制 VEGF、p-Erk 和 p-Akt 表达。对肺肿瘤组织的肿瘤组织微阵列进行的免疫组织化学检测表明，BPTF过表达预示着肺腺癌患者的不良预后。因此，我们的数据表明 BPTF 通过靶向人类肺癌中的多种信号通路，在细胞生长和存活中发挥重要作用。
BPTF, a subunit of NURF, is well known to be involved in the development of eukaryotic cell, but little is known about its roles in cancers, especially in non-small-cell lung cancer (NSCLC). Here we showed that BPTF was specifically overexpressed in NSCLC cell lines and lung adenocarcinoma tissues. Knockdown of BPTF by siRNA significantly inhibited cell proliferation, induced cell apoptosis and arrested cell cycle progress from G1 to S phase. We also found that BPTF knockdown downregulated the expression of the phosphorylated Erk1/2, PI3K and Akt proteins and induced the cleavage of caspase-8, caspase-7 and PARP proteins, thereby inhibiting the MAPK and PI3K/AKT signaling and activating apoptotic pathway. BPTF knockdown by siRNA also upregulated the cell cycle inhibitors such as p21 and p18 but inhibited the expression of cyclin D, phospho-Rb and phospho-cdc2 in lung cancer cells. Moreover, BPTF knockdown by its specific shRNA inhibited lung cancer growth in vivo in the xenografts of A549 cells accompanied by the suppression of VEGF, p-Erk and p-Akt expression. Immunohistochemical assay for tumor tissue microarrays of lung tumor tissues showed that BPTF overexpression predicted a poor prognosis in the patients with lung adenocarcinomas. Therefore, our data indicate that BPTF plays an essential role in cell growth and survival by targeting multiply signaling pathways in human lung cancers.