eIF3a Regulates Colorectal Cancer Metastasis via Translational Activation of RhoA and Cdc42.
eIF3a Regulates Colorectal Cancer Metastasis via Translational Activation of RhoA and Cdc42.
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eIF3a 通过 RhoA 和 Cdc42 的翻译激活调节结直肠癌转移
DOI：
10.3389/fcell.2022.794329
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发表时间：
2022
影响因子：
5.5
通讯作者：
Liu ZQ
中科院分区：
文献类型：
--
作者：
Mei C;Liu C;Gao Y;Dai WT;Zhang W;Li X;Liu ZQ
肿瘤转移是结直肠癌肿瘤复发和肿瘤相关死亡的主要原因，导致治疗反应差和生存率下降。EIF3a此前被描述为癌基因。然而，它在结直肠癌进展和转移中的作用还没有得到充分的研究。本研究探讨eIF3a在临床标本中的表达特异性和预测价值。分别在体内和体外验证eIF3a对细胞增殖和迁移的影响。通过Western blotting、免疫荧光、RNA结合蛋白免疫沉淀和双荧光素酶报告基因分析，揭示了其潜在的分子机制。结果表明，eIF3a在肿瘤组织中的表达明显高于癌旁正常组织。EIF3a高表达与肿瘤转移和总生存期相关。EIF3a的下调在体内外均能明显抑制肿瘤细胞的增殖和运动。在机制上，eIF3a在翻译水平上调节CDC42和RhoA的表达，进而影响伪足的形成和肌动蛋白细胞骨架的重塑。综上所述，eIF3a通过在翻译水平激活CDC42和RhoA的表达来加速癌细胞迁移表型的获得。我们的研究确定eIF3a是抑制结直肠癌转移的一个有前景的靶点。
Tumor metastasis is the major cause of tumor relapse and cancer-associated mortality in colorectal cancer, leading to poor therapeutic responses and reduced survival. eIF3a was previously described as an oncogene. However, its role in colorectal cancer progression and metastasis has not yet been fully investigated. In this study, the expression specificity and predictive value of eIF3a were investigated in clinical samples. The effects of eIF3a on cell proliferation and migration were verified in vivo and in vitro, respectively. The underlying molecular mechanism was revealed by western blotting, immunofluorescence, RNA-binding protein immunoprecipitation, and dual-luciferase reporter gene assays. The results showed that eIF3a was significantly overexpressed in tumor tissues compared with adjacent normal tissues. High eIF3a expression was correlated with tumor metastasis and overall survival. Downregulation of eIF3a obviously inhibited the proliferation and motility of malignant cells in vitro and in vivo. Mechanistically, eIF3a regulates Cdc42 and RhoA expression at the translation level, which further affects pseudopodia formation and actin cytoskeleton remodeling. Taken together, eIF3a accelerates the acquisition of the migratory phenotype of cancer cells by activating Cdc42 and RhoA expression at the translational level. Our study identified eIF3a as a promising target for inhibiting colorectal cancer metastasis.
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影响因子：
3.9
作者：
Luo CH;Zhao M;Chen XY;Shahabi S;Qiang W;Zeng L;Wang J;Zhou HH
通讯作者：
Zhou HH
DOI：
10.1083/jcb.201612069
发表时间：
2018-02-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lawson CD;Ridley AJ
通讯作者：
Ridley AJ
影响因子：
6.6
作者：
Chang, Bei;Svoboda, Kathy K. H.;Liu, Xiaohua
通讯作者：
Liu, Xiaohua
eIF3a通过调节DSB DNA修复对蒽环类化疗耐药的影响
影响因子：
5.8
作者：
Chen, Juan;Liu, Jun-Yan;Yin, Ji-Ye
通讯作者：
Yin, Ji-Ye
影响因子：
7.5
作者：
Jacquemet, Guillaume;Hamidi, Hellyeh;Ivaska, Johanna
通讯作者：
Ivaska, Johanna