Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
Mol Carcinog. 2019 Jan;58(1):126-134. doi: 10.1002/mc.22914. Epub 2018 Oct 9.
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 GSK3β phosphorylation and upregulated the levels of active β-catenin, Wnt targets c-myc, cyclin D1, and MMP7. Besides, the CCDC85B-induced upregulation of phosphorylated GSK3β and active β-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/GSK3β/β-catenin oncogenic signaling pathway. Therefore, CCDC85B might serve as a novel target for NSCLC treatment.
卷曲螺旋结构域蛋白 85B(CCDC85B)参与多种生物学过程;然而,其在人类癌症中的表达模式和功能尚不清楚。本研究表明,非小细胞肺癌(NSCLC)肿瘤细胞细胞质中 CCDC85B 的表达明显高于相邻正常肺组织(P<0.05)。此外,CCDC85B 的表达与 NSCLC 的晚期 TNM 分期(P=0.004)和阳性区域淋巴结转移(P=0.009)相关。此外,在 A549 和 H1299 肺癌细胞系中,CCDC85B 的过表达促进了细胞增殖和侵袭,而 siRNA 介导的 CCDC85B 敲低则表现出相反的效果。CCDC85B 促进 AKT 和 GSK3β 的磷酸化,并上调活性 β-连环蛋白、Wnt 靶基因 c-myc、周期蛋白 D1 和 MMP7 的水平。此外,在用 PI3K 抑制剂 LY294002 处理后,CCDC85B 诱导的磷酸化 GSK3β 和活性 β-连环蛋白的上调得到挽救。总之,CCDC85B 与 NSCLC 的进展有关,因为它通过激活 AKT/GSK3β/β-连环蛋白致癌信号通路促进肺癌细胞的增殖和侵袭。因此,CCDC85B 可能成为 NSCLC 治疗的新靶点。