雷帕霉素抑制 FBXW7 缺失诱导的结直肠癌细胞上皮-间充质转化和癌症干细胞样特征。
Rapamycin inhibits FBXW7 loss-induced epithelial-mesenchymal transition and cancer stem cell-like characteristics in colorectal cancer cells.
机构信息
Department of Anatomy and Key Laboratory of Experimental Teratology, Ministry of Education, Shandong University School of Medicine, 44 Wenhuaxilu, Jinan, Shandong 250012, PR China.
出版信息
Biochem Biophys Res Commun. 2013 May 3;434(2):352-6. doi: 10.1016/j.bbrc.2013.03.077. Epub 2013 Apr 2.
Abstract
Increased cell migration and invasion lead to cancer metastasis and are crucial to cancer prognosis. In this study, we explore whether FBXW7 plays any role in metastatic process. We show that depletion of FBXW7 induces epithelial-mesenchymal transition (EMT) in human colon cancer cells along with the increase in cell migration and invasion. Moreover, FBXW7 deficiency promotes the generation of colon cancer stem-like cells in tumor-sphere culture. mTOR inhibition by rapamycin suppresses FBXW7 loss-driven EMT, invasion and stemness. Our results define the FBXW7/mTOR axis as a novel EMT pathway that mediates cancer invasion.
摘要
细胞迁移和侵袭的增加导致癌症转移，这对癌症预后至关重要。在这项研究中，我们探讨了 FBXW7 是否在转移过程中发挥作用。我们发现，FBXW7 的耗竭会诱导人结肠癌细胞发生上皮-间充质转化（EMT），同时增加细胞迁移和侵袭。此外，FBXW7 缺失促进了肿瘤球培养中结肠癌细胞癌干细胞样特性的产生。雷帕霉素抑制 mTOR 可抑制 FBXW7 缺失驱动的 EMT、侵袭和干性。我们的结果定义了 FBXW7/mTOR 轴作为一种新的 EMT 途径，介导癌症侵袭。
相似文献
1
Rapamycin inhibits FBXW7 loss-induced epithelial-mesenchymal transition and cancer stem cell-like characteristics in colorectal cancer cells.雷帕霉素抑制 FBXW7 缺失诱导的结直肠癌细胞上皮-间充质转化和癌症干细胞样特征。
Biochem Biophys Res Commun. 2013 May 3;434(2):352-6. doi: 10.1016/j.bbrc.2013.03.077. Epub 2013 Apr 2.
2
FBXW7 suppresses epithelial-mesenchymal transition, stemness and metastatic potential of cholangiocarcinoma cells.FBXW7抑制胆管癌细胞的上皮-间质转化、干性和转移潜能。
Oncotarget. 2015 Mar 20;6(8):6310-25. doi: 10.18632/oncotarget.3355.
3
FAM83D promotes cell proliferation and motility by downregulating tumor suppressor gene FBXW7.FAM83D通过下调肿瘤抑制基因FBXW7来促进细胞增殖和运动。
Oncotarget. 2013 Dec;4(12):2476-86. doi: 10.18632/oncotarget.1581.
4
MicroRNA-25 promotes gastric cancer proliferation, invasion, and migration by directly targeting F-box and WD-40 Domain Protein 7, FBXW7.微小RNA-25通过直接靶向F盒和WD-40结构域蛋白7（FBXW7）促进胃癌的增殖、侵袭和迁移。
Tumour Biol. 2015 Sep;36(10):7831-40. doi: 10.1007/s13277-015-3510-3. Epub 2015 May 6.
5
Plk2 promotes tumor growth and inhibits apoptosis by targeting Fbxw7/Cyclin E in colorectal cancer.Plk2 通过靶向 Fbxw7/Cyclin E 在结直肠癌中促进肿瘤生长和抑制细胞凋亡。
Cancer Lett. 2016 Oct 1;380(2):457-466. doi: 10.1016/j.canlet.2016.07.004. Epub 2016 Jul 14.
6
FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression.FBXW7靶向mTOR进行降解，并在肿瘤抑制中与PTEN协同作用。
Science. 2008 Sep 12;321(5895):1499-502. doi: 10.1126/science.1162981.
7
FBXW7 negatively regulates ENO1 expression and function in colorectal cancer.FBXW7在结直肠癌中负向调控ENO1的表达及功能。
Lab Invest. 2015 Sep;95(9):995-1004. doi: 10.1038/labinvest.2015.71. Epub 2015 Jun 22.
8
Fbxw7 regulates hepatocellular carcinoma migration and invasion via Notch1 signaling pathway.Fbxw7通过Notch1信号通路调控肝细胞癌的迁移和侵袭。
Int J Oncol. 2015 Jul;47(1):231-43. doi: 10.3892/ijo.2015.2981. Epub 2015 May 4.
9
Fbxw7 regulates tumor apoptosis, growth arrest and the epithelial-to-mesenchymal transition in part through the RhoA signaling pathway in gastric cancer.Fbxw7 通过调控 RhoA 信号通路部分影响胃癌细胞的凋亡、生长抑制和上皮间质转化。
Cancer Lett. 2016 Jan 1;370(1):39-55. doi: 10.1016/j.canlet.2015.10.006. Epub 2015 Oct 13.
10
MiR-25 is up-regulated in non-small cell lung cancer and promotes cell proliferation and motility by targeting FBXW7.微小RNA-25在非小细胞肺癌中上调，并通过靶向F-Box蛋白7促进细胞增殖和迁移。
Int J Clin Exp Pathol. 2015 Aug 1;8(8):9147-53. eCollection 2015.
引用本文的文献
1
FBXW7 in gastrointestinal cancers: from molecular mechanisms to therapeutic prospects.FBXW7在胃肠道癌症中的研究：从分子机制到治疗前景
Front Pharmacol. 2024 Dec 18;15:1505027. doi: 10.3389/fphar.2024.1505027. eCollection 2024.
2
Novel Anti-Cancer Stem Cell Compounds: A Comprehensive Review.新型抗癌干细胞化合物：全面综述
Pharmaceutics. 2024 Aug 1;16(8):1024. doi: 10.3390/pharmaceutics16081024.
3
Genomic landscape and expression profile of consensus molecular subtype four of colorectal cancer.结直肠癌共识分子亚型四的基因组景观和表达谱。
Front Immunol. 2023 Jun 19;14:1160052. doi: 10.3389/fimmu.2023.1160052. eCollection 2023.
4
Targeting the biology of aging with mTOR inhibitors.用 mTOR 抑制剂靶向衰老的生物学。
Nat Aging. 2023 Jun;3(6):642-660. doi: 10.1038/s43587-023-00416-y. Epub 2023 May 4.
5
E3 ubiquitin ligases in cancer stem cells: key regulators of cancer hallmarks and novel therapeutic opportunities.E3 泛素连接酶在肿瘤干细胞中的作用：肿瘤标志物的关键调节因子和新的治疗机会。
Cell Oncol (Dordr). 2023 Jun;46(3):545-570. doi: 10.1007/s13402-023-00777-x. Epub 2023 Feb 6.
6
MECP2 promotes the migration and invasion of gastric cancer cells by modulating the Notch1/c-Myc/mTOR signaling pathways by suppressing FBXW7 transcription.MECP2通过抑制FBXW7转录来调节Notch1/c-Myc/mTOR信号通路，从而促进胃癌细胞的迁移和侵袭。
Am J Cancer Res. 2022 Nov 15;12(11):5183-5204. eCollection 2022.
7
CAR T-cells for colorectal cancer immunotherapy: Ready to go?嵌合抗原受体 T 细胞治疗结直肠癌免疫疗法：准备就绪了吗？
Front Immunol. 2022 Nov 15;13:978195. doi: 10.3389/fimmu.2022.978195. eCollection 2022.
8
Prevalence of Molecular Alterations in a Swiss Cohort of 512 Colorectal Carcinoma Patients by Targeted Next-Generation Sequencing Analysis in Routine Diagnostics.瑞士 512 例结直肠癌患者通过常规诊断中的靶向下一代测序分析的分子改变的流行率。
Pathobiology. 2023;90(3):166-175. doi: 10.1159/000526117. Epub 2022 Oct 6.
9
Peripheral tissular analysis of rapamycin's effect as a neuroprotective agent in vivo.体内分析雷帕霉素作为神经保护剂的外周组织效应。
Naunyn Schmiedebergs Arch Pharmacol. 2022 Oct;395(10):1239-1255. doi: 10.1007/s00210-022-02276-6. Epub 2022 Jul 27.
10
Multigene Panel Sequencing Reveals Cancer-Specific and Common Somatic Mutations in Colorectal Cancer Patients: An Egyptian Experience.多基因检测揭示埃及结直肠癌患者的癌症特异性和常见体细胞突变
Curr Issues Mol Biol. 2022 Mar 18;44(3):1332-1352. doi: 10.3390/cimb44030090.
本文引用的文献
1
Temporal mTOR inhibition protects Fbxw7-deficient mice from radiation-induced tumor development.短暂性抑制mTOR可保护Fbxw7基因缺陷小鼠免受辐射诱导的肿瘤发生。
Aging (Albany NY). 2013 Feb;5(2):111-9. doi: 10.18632/aging.100535.
2
Mechanisms of chemoresistance in cancer stem cells.癌症干细胞的化疗耐药机制。
Clin Transl Med. 2013 Jan 17;2(1):3. doi: 10.1186/2001-1326-2-3.
3
The mitotic kinase Aurora--a promotes distant metastases by inducing epithelial-to-mesenchymal transition in ERα(+) breast cancer cells.有丝分裂激酶 Aurora-A 通过诱导 ERα(+)乳腺癌细胞发生上皮-间充质转化促进远处转移。
Oncogene. 2014 Jan 30;33(5):599-610. doi: 10.1038/onc.2012.628. Epub 2013 Jan 21.
4
Chromosome instability modulated by BMI1-AURKA signaling drives progression in head and neck cancer.BMI1-AURKA 信号调节的染色体不稳定性驱动头颈部癌症的进展。
Cancer Res. 2013 Jan 15;73(2):953-66. doi: 10.1158/0008-5472.CAN-12-2397. Epub 2012 Nov 30.
5
MiR-25 regulates Wwp2 and Fbxw7 and promotes reprogramming of mouse fibroblast cells to iPSCs.miR-25 调控 Wwp2 和 Fbxw7，促进小鼠成纤维细胞重编程为 iPS 细胞。
PLoS One. 2012;7(8):e40938. doi: 10.1371/journal.pone.0040938. Epub 2012 Aug 17.
6
Increased efficiency in the generation of induced pluripotent stem cells by Fbxw7 ablation.通过 Fbxw7 缺失提高诱导多能干细胞的生成效率。
Genes Cells. 2012 Sep;17(9):768-77. doi: 10.1111/j.1365-2443.2012.01626.x. Epub 2012 Aug 16.
7
Proteomic screen reveals Fbw7 as a modulator of the NF-κB pathway.蛋白质组学筛选揭示 Fbw7 是 NF-κB 通路的调节剂。
Nat Commun. 2012;3:976. doi: 10.1038/ncomms1975.
8
Metastasis: The rude awakening.转移：如梦初醒。
Nature. 2012 May 30;485(7400):S55-7. doi: 10.1038/485S55a.
9
Overexpression of Aurora-A enhances invasion and matrix metalloproteinase-2 expression in esophageal squamous cell carcinoma cells.Aurora-A 的过表达增强食管鳞癌细胞的侵袭和基质金属蛋白酶-2 的表达。
Mol Cancer Res. 2012 May;10(5):588-96. doi: 10.1158/1541-7786.MCR-11-0416. Epub 2012 Apr 20.
10
Pten regulates Aurora-A and cooperates with Fbxw7 in modulating radiation-induced tumor development.PTEN 调节 Aurora-A，并与 Fbxw7 合作调节辐射诱导的肿瘤发生。
Mol Cancer Res. 2012 Jun;10(6):834-44. doi: 10.1158/1541-7786.MCR-12-0025. Epub 2012 Apr 18.
Zotero 插件