Overexpression of DTL enhances cell motility and promotes tumor metastasis in cervical adenocarcinoma by inducing RAC1-JNK-FOXO1 axis.
Overexpression of DTL enhances cell motility and promotes tumor metastasis in cervical adenocarcinoma by inducing RAC1-JNK-FOXO1 axis.
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DTL过表达通过诱导RAC1-JNK-FOXO1轴增强宫颈腺癌细胞运动并促进肿瘤转移
DOI：
10.1038/s41419-021-04179-5
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发表时间：
2021-10-11
影响因子：
9
通讯作者：
Jin Y
中科院分区：
文献类型：
--
作者：
Liu S;Gu L;Wu N;Song J;Yan J;Yang S;Feng Y;Wang Z;Wang L;Zhang Y;Jin Y
宫颈腺癌是影响年轻女性的重要疾病，死亡率高，预后差。具有致癌功能的无齿 E3 泛素蛋白连接酶同系物 (DTL) 基因已在多种癌症中进行了评估。通过本研究，我们旨在阐明DTL过度表达的宫颈腺癌的临床和分子特征，并阐明其分子机制。通过多个数据库进行生物信息学分析。 RNA测序用于获得DTL在细胞中过表达后的差异表达基因。通过体外和体内实验探讨了DTL在宫颈腺癌中的作用。我们发现 DTL 对宫颈腺癌患者具有不利的预后影响。 DTL的过表达在体外诱导肿瘤细胞的迁移和侵袭，在体内促进肺内转移。此外，DTL通过RAC1激活JNK并上调FOXO1诱导上皮间质转化以及肿瘤细胞的迁移和侵袭。因此，我们得出结论，DTL的过度表达通过调节RAC1-JNK-FOXO1轴来增强细胞运动并促进宫颈腺癌的肿瘤转移。这些结果表明DTL可能成为抗宫颈腺癌转移的潜在治疗靶点。
Cervical adenocarcinoma is an important disease that affects young women and it has a high mortality and poor prognosis. Denticleless E3 ubiquitin protein ligase homolog (DTL) gene with oncogenic function has been evaluated in several cancers. Through this study, we aimed to clarify the clinical and molecular characteristics of cervical adenocarcinoma involving overexpression of DTL and elucidate its molecular mechanism. Bioinformatics analysis was performed through multiple databases. RNA sequencing was used to obtain differentially expressed genes after DTL was overexpressed in cells. The role of DTL in cervical adenocarcinoma was explored through in vitro and in vivo experiments. We found that DTL has an unfavorable prognostic implication for patients with cervical adenocarcinoma. Overexpression of DTL induced the migration and invasion of tumor cells in vitro and promoted intra-pulmonary metastasis in vivo. In addition, DTL activated JNK through RAC1 and upregulated FOXO1 to induce epithelial–mesenchymal transition, and the migration and invasion of tumor cells. Therefore, we conclude that overexpression of DTL enhanced cell motility and promoted tumor metastasis of cervical adenocarcinoma by regulating the RAC1-JNK-FOXO1 axis. These results suggest that DTL may become a potential therapeutic target for antitumor metastasis of cervical adenocarcinoma.
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DOI：
10.1083/jcb.201305074
发表时间：
2013-10-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ponugoti B;Xu F;Zhang C;Tian C;Pacios S;Graves DT
通讯作者：
Graves DT
DOI：
10.15252/embj.201490693
发表时间：
2015-08-13
期刊：
The EMBO journal
影响因子：
--
作者：
Sahu SK;Garding A;Tiwari N;Thakurela S;Toedling J;Gebhard S;Ortega F;Schmarowski N;Berninger B;Nitsch R;Schmidt M;Tiwari VK
通讯作者：
Tiwari VK
影响因子：
16
作者：
Rossi, Mario;Duan, Shanshan;Jeong, Yeon-Tae;Horn, Moritz;Saraf, Anita;Florens, Laurence;Washburn, Michael P.;Antebi, Adam;Pagano, Michele
通讯作者：
Pagano, Michele
影响因子：
8
作者：
Mackintosh, C.;Ordonez, J. L.;de Alava, E.
通讯作者：
de Alava, E.
影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Ward, Elizabeth
通讯作者：
Ward, Elizabeth