Taniuchi Keisuke, Furihata Mutsuo, Naganuma Seiji, Dabanaka Ken, Hanazaki Kazuhiro, Saibara Toshiji
Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi UniversityNankoku, Kochi 783-8505, Japan.
Department of Endoscopic Diagnostics and Therapeutics, Kochi Medical School, Kochi UniversityNankoku, Kochi 783-8505, Japan.
Am J Cancer Res. 2018 Mar 1;8(3):387-404. eCollection 2018.
The functions of B-cell CLL/lymphoma 7B (BCL7B) are unknown and the protein lacks any known functional domains. The aim of this study was to investigate the role of BCL7B in the motility and invasiveness of pancreatic cancer cells. Immunohistochemistry was performed to determine whether high BCL7B expression in human pancreatic cancer tissues is correlated with poor prognosis. High BCL7B expression was an independent predictor of worse overall survival of pancreatic cancer patients. Immunocytochemistry showed that BCL7B was accumulated in cell protrusions of migrating pancreatic cancer cells. Knockdown of BCL7B inhibited the motility and invasiveness of pancreatic cancer cells through a decrease in cell protrusions. Phosphoprotein array analysis was performed to determine BCL7B-associated intracellular signaling pathways. Suppression of increased phosphorylated CREB expression in pancreatic cancer cells, and knockdown of promoted the motility and invasiveness by increasing cell protrusions. The combined data suggest that BCL7B promotes pancreatic cancer cell motility and invasion through a signaling pathway that involves dephosphorylation of CREB.
B 细胞慢性淋巴细胞白血病/淋巴瘤 7B(BCL7B)的功能尚不清楚,且该蛋白缺乏任何已知的功能结构域。本研究的目的是探讨 BCL7B 在胰腺癌细胞运动性和侵袭性中的作用。进行免疫组织化学以确定人胰腺癌组织中高 BCL7B 表达是否与预后不良相关。高 BCL7B 表达是胰腺癌患者总体生存较差的独立预测因素。免疫细胞化学显示 BCL7B 积聚在迁移的胰腺癌细胞的细胞突起中。敲低 BCL7B 通过减少细胞突起抑制胰腺癌细胞的运动性和侵袭性。进行磷酸化蛋白阵列分析以确定与 BCL7B 相关的细胞内信号通路。抑制胰腺癌细胞中磷酸化 CREB 表达的增加,而敲低 通过增加细胞突起促进运动性和侵袭性。综合数据表明,BCL7B 通过涉及 CREB 去磷酸化的信号通路促进胰腺癌细胞的运动性和侵袭。