Aurora B Overexpression Causes Aneuploidy and p21<sup>Cip1</sup> Repression during Tumor Development

González-Loyola, Alejandra; Fernández-Miranda, Gonzalo; Trakala, Marianna; Partida, David; Samejima, Kumiko; Ogawa, Hiromi; Cañamero, Marta; Martino, Alba De; Martínez-Ramírez, Ángel; Cárcer, Guillermo de; Castro, Ignacio Pérez de; Earnshaw, William C.; Malumbres, Marcos

doi:10.1128/mcb.01286-14

Cited by 101 publications

(90 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, overexpression of Aurora B caused defective chromosome separation leading to aneuploidy 102 . Analyses of human tumours support oncogenic roles for Aurora A and Aurora B.…”

Section: Cell Cycle Proteins and Their Role In Physiology And Cancermentioning

confidence: 99%

“…Importantly, transgenic overexpression of Aurora A in mouse mammary epithelium induced tetraploidy and centrosome amplification leading to mammary cancer formation 107 . Likewise, mice ubiquitously overexpressing Aurora B spontaneously developed lymphomas 102 . Surprisingly, despite their role as oncogenes, heterozygous deletion of the genes encoding Aurora A or Aurora B in mice also increased tumour incidence in various organs suggesting some tumour-suppressive roles 108, 109 .…”

Section: Cell Cycle Proteins and Their Role In Physiology And Cancermentioning

confidence: 99%

“… CCND1 gain:Hepatocellular carcinomas 251 Skin papillomas (DMBA) 16 B-cell lymphomas 252 Mammary cancer 13 CCND2 gain:Skin carcinomas (DMBA+TPA) 14 CCND3 gain:Skin carcinomas (DMBA+TPA) 14 Mammary cancer 253 CDK4 gain:Skin tumours (DMBA+TPA) 12, 17 Pituitary, pancreatic tumours ( Men1 +/− ) 54 Pituitary carcinomas ( Cdkn1b −/− ) 254 Endocrine tumours, haemangiomas 11 CDK6 gain:Skin papillomas (DMBA+TPA) 15 CCNE1 gain:Mammary cancer ( Trp53 +/− ) 255 Mammary cancer 45 Lung cancer 256 Lung cancer ( Kras G12D/+ ) 257 Pituitary adenomas 258 T-cell lymphomas ( Cdkn1b −/− ) 259 CCNB1/2 gain:Lung cancer 64 Skin tumours (DMBA) 64 Intestinal adenocarcinomas ( Apc Min/+ ) 64 AURKA gain:Skin carcinomas (DMBA+TPA) 260 Mammary cancer 107 AURKB gain:Lymphomas 102 Ccnd1 loss:Intestinal adenomas ( Apc Min/+ ) 261 Skin carcinomas ( v-Hras +TPA, DMBA+TPA) 262 Rhabdoid tumours ( Ini1 +/− ) 263 Mammary cancer ( Erbb2 V664D , v-Hras ) 18, 19 Mammary cancer ( Erbb2 V664D ) 22, 26 Ccnd2 loss:Intestinal adenomas ( Apc Min/+ ) 264 Ovarian, testicular, adrenal tumours ( Inha −/− ) 265 Skin carcinomas (DMBA+TPA) 14 Ccnd3 loss:

…”

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

Cell cycle proteins as promising targets in cancer therapy

2017

View full text Add to dashboard Cite

Preface Cancer is characterized by uncontrolled proliferation resulting from aberrant activity of various cell cycle proteins; therefore, cell cycle regulators are considered attractive targets in cancer therapy. Intriguingly, animal models demonstrated that some of these proteins are not essential for proliferation of non-transformed cells and development of most tissues. In contrast, many cancers are uniquely dependent on these proteins and are hence selectively sensitive to their inhibition. After decades of research on the physiological functions of cell cycle proteins and their relevance for cancer, this knowledge recently translated into the first approved cancer therapeutic targeting of a direct regulator of the cell cycle. Here, we review the role of cell cycle proteins in cancer, the rationale for targeting them in cancer treatment and results of clinical trials, as well as future therapeutic potential of various inhibitors. We focus only on proteins that directly regulate cell cycle progression. Cyclin-dependent kinases with transcriptional functions, as well as PARP inhibitors, which are highly successful in targeting BRCA1/BRCA2-mutant tumours, are not covered by this review.

show abstract

“…Also, overexpression of Aurora B caused defective chromosome separation leading to aneuploidy 102 . Analyses of human tumours support oncogenic roles for Aurora A and Aurora B.…”

Section: Cell Cycle Proteins and Their Role In Physiology And Cancermentioning

confidence: 99%

Section: Cell Cycle Proteins and Their Role In Physiology And Cancermentioning

confidence: 99%

…”

Section: Figurementioning

confidence: 99%

See 1 more Smart Citation

Cell cycle proteins as promising targets in cancer therapy

2017

View full text Add to dashboard Cite

show abstract

“…Since Plk1 is also involved in cell migration and metastasis 49 , authophagy 50 , pentose phosphate metabolism 51 or blood pressure regulation 11 53,54 ), Aurora B (Ref. 8 ), Hec1 (Ref. 55 ), UbcH10 (Ref.…”

Section: Discussionmentioning

confidence: 99%

Plk1 overexpression suppresses tumor development by inducing chromosomal instability

Cárcer

Venkateswaran

Salgueiro

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

Polo-like kinase 1 (Plk1) is a protein kinase currently considered as an attractive cancer target due to its critical role in the cell division cycle. Plk1 is overexpressed in a wide spectrum of human tumors, being frequently considered as an oncogene. However, its contribution to tumor development is unclear. Using a new inducible knock-in mouse model we report here that Plk1 overexpression does not favor cell proliferation but rather results in abnormal chromosome segregation and cytokinesis, leading to the formation of polyploid cells with reduced proliferative potential. Mechanistically, these cytokinesis defects correlate with defective loading of Cep55 and ESCRT complexes to the abscission bridge during cytokinesis in a Plk1 kinase-dependent manner. In vivo, elevated levels of Plk1 markedly prevent the development of mammary gland tumors induced either by Kras G12D or Her2, in the presence of increased rates of chromosome instability. In patients, higher Plk1 expression levels are associated with significantly increased overall survival in breast cancer subtypes. These data suggest that, despite the therapeutic benefits of inhibiting Plk1 due to its essential role in tumor cell cycles, Plk1 overexpression has tumor suppressive properties by perturbing mitotic progression and cytokinesis.

show abstract

“…Aurora B also is a protein that functions in the attachment of the mitotic spindle to the centromere. In cancerous cells, overexpression of aurora B causes unequal distribution of genetic information, creating aneuploidy cells, a hallmark of cancer . Aurora B was confirmed to be highly expressed in several malignancies and played an important role in cancer development and progression .…”

Section: Introductionmentioning

confidence: 99%

Quercetin suppresses lung cancer growth by targeting Aurora B kinase

et al. 2016

View full text Add to dashboard Cite

Abstractaurora B kinase is highly expressed in several cancer cells and promotes tumorigenesis and progression, and therefore, it is an important target for drug to treat tumors. Quercetin was identified to be an antitumor agent. Herein, we report for the first time that quercetin inhibited aurora B activities by directly binding with aurora B in vitro and in vivo. Ex vivo studies showed that quercetin inhibited aurora B activities in JB6 Cl41 cells and A549 lung cancer cells. Moreover, knockdown of aurora B in A549 cells decreased their sensitivities to quercetin. In vivo study demonstrated that injection of quercetin in A549 tumor‐bearing mice effectively suppressed cancer growth. The phosphorylation of histone 3 in tumor tissues was also decreased after quercetin treatment. In short, quercetin can suppress growth of lung cancer cells as an aurora B inhibitor both in vitro and in vivo.

show abstract

Aurora B Overexpression Causes Aneuploidy and p21^Cip1 Repression during Tumor Development

Abstract: Cip1 .

Cited by 101 publications

References 47 publications

Cell cycle proteins as promising targets in cancer therapy

Cell cycle proteins as promising targets in cancer therapy

Plk1 overexpression suppresses tumor development by inducing chromosomal instability

Quercetin suppresses lung cancer growth by targeting Aurora B kinase

Contact Info

Product

Resources

About

Aurora B Overexpression Causes Aneuploidy and p21Cip1 Repression during Tumor Development

Abstract: Cip1 .

Cited by 101 publications

References 47 publications

Cell cycle proteins as promising targets in cancer therapy

Cell cycle proteins as promising targets in cancer therapy

Plk1 overexpression suppresses tumor development by inducing chromosomal instability

Quercetin suppresses lung cancer growth by targeting Aurora B kinase

Contact Info

Product

Resources

About

Aurora B Overexpression Causes Aneuploidy and p21^Cip1 Repression during Tumor Development