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一种靶向AURKC-IκBα相互作用的小分子抑制剂可降低MDA-MB-231乳腺癌细胞的转化生长。

A small-molecule inhibitor targeting the AURKC-IκBα interaction decreases transformed growth of MDA-MB-231 breast cancer cells.

作者信息

Han Eun Hee, Min Jin-Young, Yoo Shin-Ae, Park Sung-Joon, Choe Yun-Jeong, Yun Hee Sub, Lee Zee-Won, Jin Sun Woo, Kim Hyung Gyun, Jeong Hye Gwang, Kim Hyun Kyoung, Kim Nam Doo, Chung Young-Ho

机构信息

Drug & Disease Target Research Team, Division of Bioconvergence Analysis, Korea Basic Science Institute (KBSI), Cheongju 28119, South Korea.

Immunotherapy Convergence Research Center, Korean Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, South Korea.

出版信息

Oncotarget. 2017 Jun 29;8(41):69691-69708. doi: 10.18632/oncotarget.18883. eCollection 2017 Sep 19.

DOI:10.18632/oncotarget.18883
PMID:29050234
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5642509/
Abstract

The Aurora kinases, Aurora A (AURKA), Aurora B (AURKB), and Aurora C (AURKC), are serine/threonine kinases required for the control of mitosis (AURKA and AURKB) or meiosis (AURKC). Several Aurora kinase inhibitors are being investigated as novel anticancer therapeutics. Recent studies demonstrated that AURKC activation contributes to breast cancer cell transformation. Therefore, AURKC is both a promising marker and therapeutic target for breast cancer; however, its signaling network has not been fully characterized. Using translocation-based cellular assays, we identified IκBα as a binding partner of AURKC, and found that AURKC phosphorylates IκBα at Ser32, thereby activating it. modeling and computational analyses revealed a small-molecule inhibitor (AKCI) that blocked the AURKC-IκBα interaction and exerted antitumor activity in MDA-MB-231 breast cancer cells. Specifically, AKCI induced G2/M cell-cycle arrest through modulation of the p53/p21/CDC2/cyclin B1 pathways. In addition, the drug significantly inhibited MDA-MB-231 cell migration and invasion, as well as decreasing colony formation and tumor growth. Via its interaction with IκBα, AURKC indirectly induced NF-κB activation; accordingly, AKCI decreased PMA-induced activation of NF-κB. Thus, the small-molecule inhibitor AKCI represents a first step towards developing targeted inhibitors of AURKC protein binding, which may lead to further advances in the treatment of breast cancer.

摘要

极光激酶，即极光A（AURKA）、极光B（AURKB）和极光C（AURKC），是控制有丝分裂（AURKA和AURKB）或减数分裂（AURKC）所需的丝氨酸/苏氨酸激酶。几种极光激酶抑制剂正在作为新型抗癌疗法进行研究。最近的研究表明，AURKC激活有助于乳腺癌细胞转化。因此，AURKC既是一种有前景的乳腺癌标志物，也是治疗靶点；然而，其信号网络尚未完全阐明。利用基于易位的细胞分析，我们鉴定出IκBα是AURKC的结合伴侣，并发现AURKC在Ser32位点磷酸化IκBα，从而激活它。建模和计算分析揭示了一种小分子抑制剂（AKCI），它能阻断AURKC与IκBα的相互作用，并在MDA-MB-231乳腺癌细胞中发挥抗肿瘤活性。具体而言，AKCI通过调节p53/p21/CDC2/细胞周期蛋白B1途径诱导G2/M期细胞周期阻滞。此外，该药物显著抑制MDA-MB-231细胞的迁移和侵袭，同时减少集落形成和肿瘤生长。通过与IκBα相互作用，AURKC间接诱导NF-κB激活；因此，AKCI降低了佛波酯（PMA）诱导的NF-κB激活。因此，小分子抑制剂AKCI代表了开发AURKC蛋白结合靶向抑制剂的第一步，这可能会推动乳腺癌治疗取得进一步进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/659e/5642509/4ffcf815a0fb/oncotarget-08-69691-g007a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/659e/5642509/7ccabf8bc2fe/oncotarget-08-69691-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/659e/5642509/cc4a49968877/oncotarget-08-69691-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/659e/5642509/ed63fe0792b5/oncotarget-08-69691-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/659e/5642509/de8c91e3c768/oncotarget-08-69691-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/659e/5642509/822ee0f6fc65/oncotarget-08-69691-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/659e/5642509/6416419c677e/oncotarget-08-69691-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/659e/5642509/4ffcf815a0fb/oncotarget-08-69691-g007a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/659e/5642509/7ccabf8bc2fe/oncotarget-08-69691-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/659e/5642509/cc4a49968877/oncotarget-08-69691-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/659e/5642509/ed63fe0792b5/oncotarget-08-69691-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/659e/5642509/de8c91e3c768/oncotarget-08-69691-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/659e/5642509/822ee0f6fc65/oncotarget-08-69691-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/659e/5642509/6416419c677e/oncotarget-08-69691-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/659e/5642509/4ffcf815a0fb/oncotarget-08-69691-g007a.jpg

相似文献

[1]
A small-molecule inhibitor targeting the AURKC-IκBα interaction decreases transformed growth of MDA-MB-231 breast cancer cells.

Oncotarget. 2017-6-29

[2]
The investigational Aurora kinase A inhibitor alisertib (MLN8237) induces cell cycle G2/M arrest, apoptosis, and autophagy via p38 MAPK and Akt/mTOR signaling pathways in human breast cancer cells.

Drug Des Devel Ther. 2015-3-16

[3]
Maternally recruited Aurora C kinase is more stable than Aurora B to support mouse oocyte maturation and early development.

Proc Natl Acad Sci U S A. 2012-7-9

[4]
The pan-inhibitor of Aurora kinases danusertib induces apoptosis and autophagy and suppresses epithelial-to-mesenchymal transition in human breast cancer cells.

Drug Des Devel Ther. 2015-2-17

[5]
Functions of Aurora kinase C in meiosis and cancer.

Front Cell Dev Biol. 2015-8-20

[6]
The aurora kinases in cell cycle and leukemia.

Oncogene. 2015-1-29

[7]
AMG 900, pan-Aurora kinase inhibitor, preferentially inhibits the proliferation of breast cancer cell lines with dysfunctional p53.

Breast Cancer Res Treat. 2013-10-5

[8]
Transcriptome analysis of the cancer/testis genes, DAZ1, AURKC, and TEX101, in breast tumors and six breast cancer cell lines.

Tumour Biol. 2015-9

[9]
Novel signaling molecules implicated in tumor-associated fatty acid synthase-dependent breast cancer cell proliferation and survival: Role of exogenous dietary fatty acids, p53-p21WAF1/CIP1, ERK1/2 MAPK, p27KIP1, BRCA1, and NF-kappaB.

Int J Oncol. 2004-3

[10]
Association of the AURKA and AURKC gene polymorphisms with an increased risk of gastric cancer.

IUBMB Life. 2016-8

引用本文的文献

[1]
AURKB promotes immunogenicity and immune infiltration in clear cell renal cell carcinoma.

Discov Oncol. 2024-7-16

[2]
Co-relation with novel phosphorylation sites of IκBα and necroptosis in breast cancer cells.

BMC Cancer. 2021-5-24

[3]
: a promising biomarker in clear cell renal cell carcinoma.

PeerJ. 2019-9-16

[4]
Mitochondria-targeted antioxidant SkQ1 suppresses fibrosarcoma and rhabdomyosarcoma tumour cell growth.

Cell Cycle. 2018-7-31

本文引用的文献

[1]
State-of-the-art strategies for targeting protein-protein interactions by small-molecule inhibitors.

Chem Soc Rev. 2015-8-6

[2]
Transcriptome analysis of the cancer/testis genes, DAZ1, AURKC, and TEX101, in breast tumors and six breast cancer cell lines.

Tumour Biol. 2015-9

[3]
The investigational Aurora kinase A inhibitor alisertib (MLN8237) induces cell cycle G2/M arrest, apoptosis, and autophagy via p38 MAPK and Akt/mTOR signaling pathways in human breast cancer cells.

Drug Des Devel Ther. 2015-3-16

[4]
Small-molecule inhibitors of protein-protein interactions: progressing toward the reality.

Chem Biol. 2014-9-18

[5]
The aurora kinases in cell cycle and leukemia.

Oncogene. 2015-1-29

[6]
Selective disruption of aurora C kinase reveals distinct functions from aurora B kinase during meiosis in mouse oocytes.

PLoS Genet. 2014-2-27

[7]
Targeting the epigenetic machinery of cancer cells.

Oncogene. 2014-1-27

[8]
Targeting protein-protein interaction by small molecules.

Annu Rev Pharmacol Toxicol. 2013-10-21

[9]
The complexity of NF-κB signaling in inflammation and cancer.

Mol Cancer. 2013-8-2

[10]
Targeting protein-protein interactions as an anticancer strategy.

Trends Pharmacol Sci. 2013-5-29

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