CCDC85B promotes non-small cell lung cancer cell proliferation and invasion
CCDC85B promotes non-small cell lung cancer cell proliferation and invasion
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DOI：
10.1002/mc.22914
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发表时间：
2019-01-01
影响因子：
4.6
通讯作者：
Wang, Enhua
中科院分区：
文献类型：
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作者：
Feng, Yangyang;Gao, Yue;Wang, Enhua
含有85B的线圈结构域（CCDC85B）参与多种生物过程；然而，其在人类癌症中的表达模式和功能尚不清楚。本研究发现，CCDC85B在非小细胞肺癌（NSCLC）肿瘤细胞细胞质中的表达明显高于邻近正常肺组织（P < 0.05）。此外，CCDC85B表达与NSCLC TNM晚期（P = 0.004）和区域淋巴结转移阳性（P = 0.009）相关。此外，在A549和H1299肺癌细胞系中，CCDC85B过表达促进细胞增殖和侵袭，而sirna介导的CCDC85B敲低则表现出相反的作用。CCDC85B促进AKT和GSK3 β磷酸化，上调活性β -连环蛋白、Wnt靶点c-myc、cyclin D1和MMP7的水平。此外，在pi3k抑制剂LY294002治疗后，ccdc85b诱导的磷酸化GSK3 β和活性β -连环蛋白上调得以恢复。综上所述，CCDC85B通过激活AKT/GSK3 β / β -catenin致癌信号通路促进肺癌细胞的增殖和侵袭，与NSCLC进展相关。因此，CCDC85B可能成为NSCLC治疗的新靶点。
Coiled-coil domain containing 85 B (CCDC85B) is involved in diverse biological processes; however, its expression patterns and functions in human cancers are yet unknown. The present study demonstrated that the expression of CCDC85B in the cytoplasm of the non-small cell lung cancer (NSCLC) tumor cells was significantly higher compared to adjacent normal lung tissues (P < 0.05). Furthermore, CCDC85B expression correlated with advanced TNM stage (P = 0.004) and positive regional lymph node metastasis (P = 0.009) of NSCLC. In addition, in A549 and H1299 lung cancer cell lines, the overexpression of CCDC85B promoted cell proliferation and invasion, while siRNA-mediated CCDC85B knockdown exhibited opposite effects. CCDC85B promoted AKT and GSK3 beta phosphorylation and upregulated the levels of active beta-catenin, Wnt targets c-myc, cyclin D1, and MMP7. Besides, the CCDC85B-induced upregulation of phosphorylated GSK3 beta and active beta-catenin was rescued following the treatment with PI3 K inhibitor, LY294002. In conclusion, CCDC85B was associated with NSCLC progression as it promoted the proliferation and invasion of lung cancer cells through activated AKT/GSK3 beta/beta-catenin oncogenic signaling pathway. Therefore, CCDC85B might serve as a novel target for NSCLC treatment.