EIF5A2 controls ovarian tumor growth and metastasis by promoting epithelial to mesenchymal transition via the TGFβ pathway.
EIF5A2 controls ovarian tumor growth and metastasis by promoting epithelial to mesenchymal transition via the TGFβ pathway.
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EIF5A2通过转化生长因子β途径促进上皮细胞向间充质细胞转化，从而控制卵巢肿瘤的生长和转移。
DOI：
10.1186/s13578-021-00578-5
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发表时间：
2021-04-07
影响因子：
7.5
通讯作者：
Yue J
中科院分区：
文献类型：
--
作者：
Zhao G;Zhang W;Dong P;Watari H;Guo Y;Pfeffer LM;Tigyi G;Yue J
上皮间质转化（EMT）有助于肿瘤转移和化疗耐药。真核起始因子 5A2 (EIF5A2) 在多种人类癌症中高度表达，但在正常组织中很少表达。虽然 EIF5A2 在多种癌症中具有致癌活性并有助于肿瘤转移，但其在卵巢癌中的作用尚不清楚。在本研究中，我们研究EIF5A2是否通过促进EMT促进卵巢肿瘤转移。为了研究 EIF5A2 的作用，我们使用慢病毒 CRISPR/Cas9 切口酶在高侵袭性 SKOV3 和 OVCAR8 细胞中敲除 (KO) EIF5A2，并使用慢病毒载体在低侵袭性 OVCAR3 细胞中过表达 EIF5A2。在体外检查卵巢癌细胞的细胞增殖、迁移和侵袭，并使用原位卵巢癌小鼠模型在体内评估肿瘤转移。在此，我们报告 EIF5A2 在卵巢癌中高表达，并与患者的不良生存率相关。慢病毒 CRISPR/Cas9 切口酶载体介导的 EIF5A2 敲除 (KO) 可抑制表达高水平 EIF5A2 的 SKOV3 和 OVCAR8 卵巢癌细胞中的上皮间质转化 (EMT)。相反，EIF5A2 的过表达会促进表达相对较低 EIF5A2 水平的 OVCAR3 上皮腺癌细胞中的 EMT。 SKOV3和OVCAR8细胞中EIF5A2的KO可抑制卵巢癌细胞的迁移和侵袭，而其过表达可促进OVCAR3腺癌细胞中的细胞迁移和侵袭。我们进一步证明EIF5A2通过激活TGFβ途径促进EMT，并且在原位卵巢癌小鼠模型中敲除EIF5A2可抑制卵巢肿瘤的生长和转移。我们的结果表明EIF5A2通过促进EMT和激活TGFβ途径是卵巢肿瘤生长和转移的重要控制器。在线版本包含可在 10.1186/s13578-021-00578-5 获取的补充材料。
Epithelial to mesenchymal transition (EMT) contributes to tumor metastasis and chemoresistance. Eukaryotic initiation factor 5A2 (EIF5A2) is highly expressed in a variety of human cancers but rarely expressed in normal tissues. While EIF5A2 has oncogenic activity in several cancers and contributes to tumor metastasis, its role in ovarian cancer is unknown. In this study, we investigate whether EIF5A2 contributes to ovarian tumor metastasis by promoting EMT. To investigate the role of EIF5A2, we knocked out (KO) EIF5A2 using lentiviral CRISPR/Cas9 nickase in high invasive SKOV3 and OVCAR8 cells and overexpressed EIF5A2 in low invasive OVCAR3 cells using lentiviral vector. Cell proliferation, migration and invasion was examined in vitro ovarian cancer cells and tumor metastasis was evaluated in vivo using orthotopic ovarian cancer mouse models. Here we report that EIF5A2 is highly expressed in ovarian cancers and associated with patient poor survival. Lentiviral CRISPR/Cas9 nickase vector mediated knockout (KO) of EIF5A2 inhibits epithelial to mesenchymal transition (EMT) in SKOV3 and OVCAR8 ovarian cancer cells that express high levels of EIF5A2. In contrast, overexpression of EIF5A2 promotes EMT in OVCAR3 epithelial adenocarcinoma cells that express relatively low EIF5A2 levels. KO of EIF5A2 in SKOV3 and OVCAR8 cells inhibits ovarian cancer cell migration and invasion, while its overexpression promotes cell migration and invasion in OVCAR3 adenocarcinoma cells. We further demonstrate that EIF5A2 promotes EMT by activating the TGFβ pathway and KO of EIF5A2 inhibits ovarian tumor growth and metastasis in orthotopic ovarian cancer mouse models. Our results indicate that EIF5A2 is an important controller of ovarian tumor growth and metastasis by promoting EMT and activating the TGFβ pathway. The online version contains supplementary material available at 10.1186/s13578-021-00578-5.
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影响因子：
3.7
作者：
Chen Z;Wang Y;Liu W;Zhao G;Lee S;Balogh A;Zou Y;Guo Y;Zhang Z;Gu W;Li C;Tigyi G;Yue J
通讯作者：
Yue J
影响因子：
1.8
作者：
Shek FH;Fatima S;Lee NP
通讯作者：
Lee NP
影响因子：
3.7
作者：
Hussey GS;Link LA;Brown AS;Howley BV;Chaudhury A;Howe PH
通讯作者：
Howe PH
影响因子：
4.8
作者：
Fujimura, Ken;Choi, Sunkyu;Klemke, Richard
通讯作者：
Klemke, Richard
影响因子：
4.4
作者：
Jenkins, ZA;Hååg, PG;Johansson, HE
通讯作者：
Johansson, HE