Aurora kinase A inhibition-induced autophagy triggers drug resistance in breast cancer cells

Zou, Zhengzhi; Yuan, Zhongyu; Zhang, Qiongxia; Long, Zi‐Jie; Chen, Jinna; Tang, Zhe; Zhu, Yuliang; Chen, Shupeng; Xu, Jie; Yan, Min; Wang, Jing; Liu, Quentin

doi:10.4161/auto.22110

Cited by 154 publications

(129 citation statements)

References 56 publications

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“…mTORC1 activation inhibited autophagy by abolishing phosphorylated ATG13 protein binding to ATG1, promoting the accumulation of p62 protein via reducing its degradation (59). Indeed, decrease the p62 expression by mTOR inhibitor was showed in some reports (8,60). Similarly, we found that expression of p62 decreased in mTOR inhibitors treated polyploidy cells (Fig.…”

Section: Discussionsupporting

confidence: 61%

“…5). We previously showed that Aurora inhibition induced autophagy and triggered drug resistance, which could be reversed by autophagy inhibitors (8). These paradoxical data suggested that cell death or survival promoted by autophagy depended on the physiologic state of the cell (47).…”

Section: Discussionmentioning

confidence: 99%

“…Although Aurora kinases inhibitors have significant therapeutic potential in AML, single-agent activity seems to be uniformly modest and the efficacy needs improving (6). Recently, we also showed that Aurora A inhibition triggered drug resistance could be reversed by autophagy inhibitors in breast cancer cells (8). In addition, combination of Aurora kinases inhibitors with vincristine or dasatinib presented synergistic effect to inhibit cell viability in human pre-B acute lymphoblastic leukemia (9).…”

Section: Introductionmentioning

confidence: 90%

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Inhibition of mTOR Pathway Sensitizes Acute Myeloid Leukemia Cells to Aurora Inhibitors by Suppression of Glycolytic Metabolism

Liu

Long

Wang

et al. 2013

Molecular Cancer Research

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Aurora kinases are overexpressed in large numbers of tumors and considered as potential therapeutic targets. In this study, we found that the Aurora kinases inhibitors MK-0457 (MK) and ZM447439 (ZM) induced polyploidization in acute myeloid leukemia (AML) cell lines. The level of glycolytic metabolism was significantly increased in the polyploidy cells, which were sensitive to glycolysis inhibitor 2-deoxy-D-glucose (2DG), suggesting that polyploidy cells might be eliminated by metabolism deprivation. Indeed, inhibition of mTOR pathway by mTOR inhibitors (rapamycin and PP242) or 2DG promoted not only apoptosis but also autophagy in the polyploidy cells induced by Aurora inhibitors. Mechanically, PP242 or2DGdecreased the level of glucose uptake and lactate production in polyploidy cells as well as the expression of p62/SQSTM1. Moreover, knockdown of p62/ SQSTM1 sensitized cells to the Aurora inhibitor whereas overexpression of p62/SQSTM1 reduced drug efficacy. Thus, our results revealed that inhibition of mTOR pathway decreased the glycolytic metabolism of the polyploidy cells, and increased the efficacy of Aurora kinases inhibitors, providing a novel approach of combination treatment in AML. Mol Cancer Res; 11(11); 1326-36. Ó2013 AACR.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

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Inhibition of mTOR Pathway Sensitizes Acute Myeloid Leukemia Cells to Aurora Inhibitors by Suppression of Glycolytic Metabolism

Liu

Long

Wang

et al. 2013

Molecular Cancer Research

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“…Polymorphisms in the AURKA gene have been shown to increase the risk of primary breast cancer (26). Studies have revealed that the increased expression of AURKA is associated with laryngeal, nasopharyngeal and breast cancer metastasis (27)(28)(29)(30). AURKA has been demonstrated to be accountable for the phosphorylation of Breast Cancer 1, Early Onset (BRCA1) (31).…”

Section: Discussionmentioning

confidence: 99%

Network analysis revealed aurora kinase dysregulation in five gynecological types of cancer

Sethi

Mishra

2017

Oncol Lett

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Abstract. Gene markers are crucial for cancer prognosis and treatment. Previous studies have placed greater emphasis on individual diagnostic genes, thereby ignoring systemic-level attributes across diseases. Female-specific cells namely, breast, endometrium, cervical, ovarian and vulvar cells are highly susceptible to cancer. To date, a limited number of molecular studies have been performed that evaluate common biological processes across gynecological types of cancer. Differentially expressed genes in breast, cervical, endometrial, vulvar and ovarian cancer were utilized to construct protein-protein interaction networks, and to identify a common module across the five cancer types. A single common module with 8 nodes and 26 edges was mined among the five cancer systems. In total, four hub genes were present across the five cancer gene sets. Genes in the common module were enriched for the common pathways and associated diseases. The aurora kinase pathway was revealed to be conserved across the five cancer types surveyed. The present study, therefore, revealed that the aurora kinase pathway has a crucial function in the pathogenesis of the five aforementioned gynecological types of cancer through cross-tumor conservation.

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“…Apoptosis is one of the main signs of effective anticancer chemotherapy; however, due to drug resistance, the apoptotic effects of drugs on the tumor cells are weakened and a large proportion of patients respond poorly to chemotherapy (19,20). At present, drug resistance of tumor cells is one of the main reasons for chemotherapy failure (21). Therefore, it is of great clinical significance to elucidate the mechanism underlying the development of drug resistance of tumor cells, in order to reverse this process and improve the sensitivity of tumor cells to chemotherapeutic agents (22).…”

Section: Mirnas and Chemotherapy For Crcmentioning

confidence: 99%

Role of microRNAs in the resistance of colorectalï¿½cancer to chemoradiotherapy (Review)

Sheng

Zhang

et al. 2018

mol clin onc

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Abstract. Colorectal cancer (CRC) is among the main tumor-related causes of death worldwide. The fact that the majority of the patients develop resistance to chemoradiotherapy (CRT) is a major obstacle for the treatment of CRC. In order to develop more effective treatment strategies, it is crucial to elucidate the mechanisms underlying the development of resistance to CRT. Several studies have recently indicated the regulatory effects of microRNAs (miRNAs) in response to antitumor agents. For example, miR-34a attenuates the chemoresistance of colon cancer to 5-FU by inhibiting E2F3 and SIRT1. The miR-34a mimic MRX34 is the first synthetic miRNA to have been entered into clinical trials. miR-21 prevents tumor cell stemness, invasion and drug resistance, which are required for the development of CRC. These findings suggest that miRNAs represent a focus in the research of novel cancer treatments aimed at sensitizing cancer cells to chemotherapeutic drugs. The aim of the present study was to review the functions of miRNAs and investigate the roles of miRNAs in CRC radioresistance or chemoresistance. Furthermore, the potential of including miRNAs in therapeutic strategies and using them as molecular biomarkers for predicting radiosensitivity and chemosensitivity was discussed.

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Aurora kinase A inhibition-induced autophagy triggers drug resistance in breast cancer cells

Abstract: (2012) Aurora kinase A inhibition-induced autophagy triggers drug resistance in breast cancer cells,

Cited by 154 publications

References 56 publications

Inhibition of mTOR Pathway Sensitizes Acute Myeloid Leukemia Cells to Aurora Inhibitors by Suppression of Glycolytic Metabolism

Inhibition of mTOR Pathway Sensitizes Acute Myeloid Leukemia Cells to Aurora Inhibitors by Suppression of Glycolytic Metabolism

Network analysis revealed aurora kinase dysregulation in five gynecological types of cancer

Role of microRNAs in the resistance of colorectalï¿½cancer to chemoradiotherapy (Review)

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