Lentiviral vector mediated-ASAP1 expression promotes epithelial to mesenchymal transition in ovarian cancer cells

Lentiviral vector mediated-ASAP1 expression promotes epithelial to mesenchymal transition in ovarian cancer cells
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DOI:
10.3892/ol.2018.7834
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发表时间:
2018-04-01
期刊:
影响因子:
2.9
通讯作者:
Yue, Junming
Yue, Junming
中科院分区:
医学4区
文献类型:
--
作者:
Zhang, Tao;Zhao, Guannan;Yue, Junming

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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,具有很高的死亡率。ASAP1 (ArfGAP与SH3结构域、锚定蛋白重复序列和PH结构域1)是一种adp核糖基化因子gtpase激活蛋白,参与肿瘤转移。然而,ASAP1在卵巢癌中的作用是完全未知的。本研究报道ASAP1在卵巢癌中高表达,其表达与患者总体生存不良及预后呈正相关。慢病毒载体介导的ASAP1表达促进卵巢癌细胞系SKOV3和OVCAR3的细胞迁移和侵袭。此外,ASAP1促进细胞增殖和存活,抑制化疗药物紫杉醇诱导的细胞凋亡。此外,在卵巢癌细胞系中,ASAP1的表达通过上调间充质细胞标志物N-cadherin和vimentin,下调上皮细胞标志物E-cadherin,促进上皮细胞向间充质转化(EMT)。这些数据首次表明ASAP1通过促进卵巢癌细胞的EMT表现出致癌作用。
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.