Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.
Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):74-82. doi: 10.1016/j.bbrc.2018.10.164. Epub 2018 Nov 16.
Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein required for mitosis and spindle assembly. Previous studies showed that TPX2 is overexpressed in various human cancers and promotes cancer progression. In this study, the differentially expressed genes including TPX2 were screened in GEO database for gene expression microarray of breast cancer. The TPX2 expression level was significantly increased in breast cancer cells and the breast malignant tissues compared with those controls. In vitro experiment further confirmed that knockdown of TPX2 by small hairpin RNA inhibited breast cancer cell proliferatio, migration, and induced cell apoptosis. TPX2 silencing decreased the expression of PI3K and extent of AKT phosphorylation, as well as increased expression of p53 and p21. Taken together, our findings indicate that TPX2 silencing negatively regulates the PI3K/AKT and activates p53 signaling pathway by which breast cancer cells proliferation were inhibited whereas cellulars apoptosis were accelerated, suggesting that TPX2 may be a potential target for anticancer therapy in breast cancer.
靶向蛋白 Xenopus kinesin-like protein 2(TPX2)是一种微管相关蛋白,对于有丝分裂和纺锤体组装是必需的。先前的研究表明,TPX2 在各种人类癌症中过度表达,并促进癌症进展。在这项研究中,我们在 GEO 数据库中筛选了包括 TPX2 在内的差异表达基因,用于乳腺癌基因表达微阵列。与对照组相比,乳腺癌细胞和乳腺恶性组织中 TPX2 的表达水平显著增加。体外实验进一步证实,短发夹 RNA 敲低 TPX2 抑制乳腺癌细胞增殖、迁移,并诱导细胞凋亡。TPX2 沉默降低了 PI3K 的表达和 AKT 磷酸化的程度,同时增加了 p53 和 p21 的表达。总之,我们的研究结果表明,TPX2 沉默通过负调控 PI3K/AKT 并激活 p53 信号通路来抑制乳腺癌细胞的增殖,同时加速细胞凋亡,提示 TPX2 可能是乳腺癌治疗的潜在靶点。