Zhang Tao, Zhao Guannan, Yang Chuanhe, Dong Peixin, Watari Hidemichi, Zeng Lin, Pfeffer Lawrence M, Yue Junming
Laboratory Animal Center of The Academy of Military Medical Science, Beijing 100071, P.R. China.
Center for Cancer Research, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Oncol Lett. 2018 Apr;15(4):4432-4438. doi: 10.3892/ol.2018.7834. Epub 2018 Jan 22.
Ovarian cancer is one of the most common malignancies in women and has a high mortality rate due to metastatic progression and tumor recurrence. ASAP1 (ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1) is an ADP-ribosylation factor GTPase-activating protein, which is involved in tumor metastasis. However, the role of ASAP1 in ovarian cancer is completely unknown. The present study reported that ASAP1 was highly expressed in ovarian carcinoma, and expression positively-correlated with overall poor survival and prognosis of patients. Lentiviral vector mediated ASAP1 expression promoted cell migration and invasion in ovarian cancer cell lines SKOV3 and OVCAR3. In addition, ASAP1 promoted cell proliferation, survival and inhibited chemotherapy drug paclitaxel-induced cell apoptosis. Furthermore, ASAP1 expression promoted epithelial to mesenchymal transition (EMT) by upregulating the mesenchymal cell markers N-cadherin and vimentin, and downregulating epithelial cell marker E-cadherin in the ovarian cancer cell lines. The data indicate for the first time that ASAP1 exhibits an oncogenic role by promoting EMT in ovarian cancer cells.
卵巢癌是女性最常见的恶性肿瘤之一,由于转移进展和肿瘤复发,其死亡率很高。ASAP1(含SH3结构域、锚蛋白重复序列和PH结构域的ArfGAP 1)是一种ADP核糖基化因子GTP酶激活蛋白,参与肿瘤转移。然而,ASAP1在卵巢癌中的作用完全未知。本研究报道ASAP1在卵巢癌中高表达,且表达与患者总体生存不良和预后呈正相关。慢病毒载体介导的ASAP1表达促进卵巢癌细胞系SKOV3和OVCAR3中的细胞迁移和侵袭。此外,ASAP1促进细胞增殖、存活并抑制化疗药物紫杉醇诱导的细胞凋亡。此外,ASAP1表达通过上调间充质细胞标志物N-钙黏蛋白和波形蛋白,下调卵巢癌细胞系中的上皮细胞标志物E-钙黏蛋白,促进上皮-间质转化(EMT)。数据首次表明ASAP1通过促进卵巢癌细胞中的EMT发挥致癌作用。