Tang Jie, Ji Lili, Wang Yuchan, Huang Yuejiao, Yin Haibing, He Yunhua, Liu Jing, Miao Xiaobing, Wu Yaxun, Xu Xiaohong, He Song, Cheng Chun
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu Province, 226001, People's Republic of China.
Int J Hematol. 2015 Jul;102(1):25-34. doi: 10.1007/s12185-015-1783-3. Epub 2015 Mar 25.
The expression and biologic function of the gene encoding vacuolar protein sorting 4B (VPS4B) in human multiple myeloma (MM) were investigated in this study. We determined that VPS4B expression is decreased in adherent MM cells and that knockdown of VPS4B expression induces cell adhesion-mediated drug resistance (CAM-DR) in MM. This induced CAM-DR phenotype manifested through down-regulation of cell apoptosis and requires phosphorylation of AKT and Erk. Finally, VPS4B expression was positively correlated with cell proliferation. Our findings support a role for VPS4B in MM cell proliferation, adhesion, and drug resistance, and pave the way for a novel therapeutic approach targeting this molecule.
本研究调查了编码液泡蛋白分选4B（VPS4B）的基因在人多发性骨髓瘤（MM）中的表达及生物学功能。我们确定VPS4B在贴壁MM细胞中的表达降低，并且VPS4B表达的敲低诱导MM细胞发生细胞黏附介导的耐药性（CAM-DR）。这种诱导的CAM-DR表型通过细胞凋亡的下调表现出来，并且需要AKT和Erk的磷酸化。最后，VPS4B表达与细胞增殖呈正相关。我们的研究结果支持VPS4B在MM细胞增殖、黏附和耐药中发挥作用，并为靶向该分子的新型治疗方法铺平了道路。
