scholarly journals Aurora Kinase B Inhibition: A Potential Therapeutic Strategy for Cancer

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1981
Author(s):  
Naheed Arfin Borah ◽  
Mamatha M. Reddy
Keyword(s):  
Drug Resistance ◽  
Cell Cycle Progression ◽  
Therapeutic Strategy ◽  
Tumor Development ◽  
Aurora Kinase ◽  
Aurora Kinase B ◽  
Development Therapy ◽  
Chromosomal Passenger ◽  
Combination Studies ◽  
Related Drug

Aurora kinase B (AURKB) is a mitotic serine/threonine protein kinase that belongs to the aurora kinase family along with aurora kinase A (AURKA) and aurora kinase C (AURKC). AURKB is a member of the chromosomal passenger protein complex and plays a role in cell cycle progression. Deregulation of AURKB is observed in several tumors and its overexpression is frequently linked to tumor cell invasion, metastasis and drug resistance. AURKB has emerged as an attractive drug target leading to the development of small molecule inhibitors. This review summarizes recent findings pertaining to the role of AURKB in tumor development, therapy related drug resistance, and its inhibition as a potential therapeutic strategy for cancer. We discuss AURKB inhibitors that are in preclinical and clinical development and combination studies of AURKB inhibition with other therapeutic strategies.

scholarly journals Haspin inhibition reveals functional differences of interchromatid axis–localized AURKB and AURKC

2017 ◽  
Vol 28 (17) ◽  
pp. 2233-2240 ◽  
Author(s):  
Suzanne M. Quartuccio ◽  
Shweta S. Dipali ◽  
Karen Schindler
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Aurora Kinase ◽  
Genetic Abnormality ◽  
Aurora Kinase B ◽  
Kinase C ◽  
Functional Differences ◽  
Chromosomal Passenger ◽  
Functional Capacities ◽  
Meiosis I

Aneuploidy is the leading genetic abnormality contributing to infertility, and chromosome segregation errors are common during female mammalian meiosis I (MI). Previous results indicate that haspin kinase regulates resumption of meiosis from prophase arrest, chromosome condensation, and kinetochore–microtubule attachments during early prometaphase of MI. Here we report that haspin inhibition in late prometaphase I causes acceleration of MI, bypass of the spindle assembly checkpoint (SAC), and loss of interchromatid axis–localized Aurora kinase C. Meiotic cells contain a second chromosomal passenger complex (CPC) population, with Aurora kinase B (AURKB) bound to INCENP. Haspin inhibition in oocytes from Aurkc−/− mice, where AURKB is the sole CPC kinase, does not alter MI completion timing, and no change in localization of the SAC protein, MAD2, is observed. These data suggest that AURKB on the interchromatid axis is not needed for SAC activation and illustrate a key difference between the functional capacities of the two AURK homologues.

scholarly journals Aurkb/PP1-mediated resetting of Oct4 during the cell cycle determines the identity of embryonic stem cells

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Jihoon Shin ◽  
Tae Wan Kim ◽  
Hyunsoo Kim ◽  
Hye Ji Kim ◽  
Min Young Suh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Cycle Progression ◽  
Embryonic Stem ◽  
Aurora Kinase ◽  
Cycle Progression ◽  
Aurora Kinase B ◽  
Somatic Cell Reprogramming ◽  
M Phase

Pluripotency transcription programs by core transcription factors (CTFs) might be reset during M/G1 transition to maintain the pluripotency of embryonic stem cells (ESCs). However, little is known about how CTFs are governed during cell cycle progression. Here, we demonstrate that the regulation of Oct4 by Aurora kinase b (Aurkb)/protein phosphatase 1 (PP1) during the cell cycle is important for resetting Oct4 to pluripotency and cell cycle genes in determining the identity of ESCs. Aurkb phosphorylates Oct4(S229) during G2/M phase, leading to the dissociation of Oct4 from chromatin, whereas PP1 binds Oct4 and dephosphorylates Oct4(S229) during M/G1 transition, which resets Oct4-driven transcription for pluripotency and the cell cycle. Aurkb phosphor-mimetic and PP1 binding-deficient mutations in Oct4 alter the cell cycle, effect the loss of pluripotency in ESCs, and decrease the efficiency of somatic cell reprogramming. Our findings provide evidence that the cell cycle is linked directly to pluripotency programs in ESCs.

scholarly journals Regulator of Chromosome Condensation 2 Modulates Cell Cycle Progression, Tumorigenesis, and Therapeutic Resistance

2021 ◽  
Vol 7 ◽  
Author(s):  
Kun Guo ◽  
Cheng Zhao ◽  
Bin Lang ◽  
Huiqin Wang ◽  
Hang Zheng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
G Proteins ◽  
Cell Cycle Progression ◽  
Tumor Development ◽  
Chromosome Condensation ◽  
Therapeutic Resistance ◽  
Cycle Progression ◽  
Guanine Exchange Factor ◽  
Chromosomal Passenger ◽  
Regulation Of Cell Cycle

Accurate regulation of cell cycle is important for normal tissue development and homeostasis. RCC2 (Regulator of Chromosome Condensation 2) play a role as chromosomal passenger complex (CPC) implicated in all cell cycle phases. RCC2 was initially identified as Ran guanine exchange factor (GEF) for small G proteins. Therefore, RCC2 plays a key role in oncogenesis of most cancers. RCC2 is implicated in Colorectal Cancer (CRC), Lung Adenocarcinoma (LUAD), breast cancer, and ovarian cancer. Expression level of RCC2 protein determines regulation of tumor cell proliferation, invasion, metastasis, and radio-chemotherapeutic resistance. In this review, we explored proteins that interact with RCC2 to modulate tumor development and cancer therapeutic resistance by regulation of cell cycle process through various signaling pathways.

scholarly journals Aurora B Overexpression Causes Aneuploidy and p21Cip1Repression during Tumor Development

2015 ◽  
Vol 35 (20) ◽  
pp. 3566-3578 ◽  
Author(s):  
Alejandra González-Loyola ◽  
Gonzalo Fernández-Miranda ◽  
Marianna Trakala ◽  
David Partida ◽  
Kumiko Samejima ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Cultured Cells ◽  
Tumor Development ◽  
Inverse Correlation ◽  
Aurora Kinase ◽  
Tumor Formation ◽  
Aurora B ◽  
Aurora Kinase B

Aurora kinase B, one of the three members of the mammalian Aurora kinase family, is the catalytic component of the chromosomal passenger complex, an essential regulator of chromosome segregation in mitosis. Aurora B is overexpressed in human tumors although whether this kinase may function as an oncogenein vivois not established. Here, we report a new mouse model in which expression of the endogenousAurkblocus can be inducedin vitroandin vivo. Overexpression of Aurora B in cultured cells induces defective chromosome segregation and aneuploidy. Long-term overexpression of Aurora Bin vivoresults in aneuploidy and the development of multiple spontaneous tumors in adult mice, including a high incidence of lymphomas. Overexpression of Aurora B also results in a reduced DNA damage response and decreased levels of the p53 target p21Cip1in vitroandin vivo, in line with an inverse correlation between Aurora B and p21Cip1expression in human leukemias. Thus, overexpression of Aurora B may contribute to tumor formation not only by inducing chromosomal instability but also by suppressing the function of the cell cycle inhibitor p21Cip1.

Methods to unravel the role of HDAC10 in autophagy-related drug resistance

2015 ◽  
Vol 227 (06/07) ◽  
Author(s):  
J Fabian ◽  
J Ridinger ◽  
O Witt ◽  
I Oehme
Keyword(s):  
Drug Resistance ◽  
Related Drug

Interrupting the FGF19-FGFR4 Axis to Therapeutically Disrupt Cancer Progression

2018 ◽  
Vol 19 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Liwei Lang ◽  
Austin Y. Shull ◽  
Yong Teng
Keyword(s):  
Cancer Progression ◽  
Therapeutic Strategy ◽  
Tumor Development ◽  
Vital Role ◽  
Signaling Cascades ◽  
Cancer Cell Proliferation ◽  
Clinical Use ◽  
Fibroblast Growth ◽  
Apoptosis Resistance ◽  
Downstream Signaling

Coordination between the amplification of the fibroblast growth factor FGF19, overexpression of its corresponding receptor FGFR4, and hyperactivation of the downstream transmembrane enzyme β-klotho has been found to play pivotal roles in mediating tumor development and progression. Aberrant FGF19-FGFR4 signaling has been implicated in driving specific tumorigenic events including cancer cell proliferation, apoptosis resistance, and metastasis by activating a myriad of downstream signaling cascades. As an attractive target, several strategies implemented to disrupt the FGF19-FGFR4 axis have been developed in recent years, and FGF19-FGFR4 binding inhibitors are being intensely evaluated for their clinical use in treating FGF19-FGFR4 implicated cancers. Based on the established work, this review aims to detail how the FGF19-FGFR4 signaling pathway plays a vital role in cancer progression and why disrupting communication between FGF19 and FGFR4 serves as a promising therapeutic strategy for disrupting cancer progression.

scholarly journals Inhibition of Aurora Kinase B activity disrupts development and differentiation of salivary glands

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Abeer K. Shaalan ◽  
Tathyane H. N. Teshima ◽  
Abigail S. Tucker ◽  
Gordon B. Proctor
Keyword(s):  
Cell Cycle ◽  
Embryonic Development ◽  
Salivary Glands ◽  
Aurora Kinase ◽  
Serine Threonine Kinase ◽  
Aurora Kinase B ◽  
Development And Differentiation ◽  
Differentiation Marker ◽  
Key Events

AbstractLittle is known about the key molecules that regulate cell division during organogenesis. Here we determine the role of the cell cycle promoter aurora kinase B (AURKB) during development, using embryonic salivary glands (E-SGs) as a model. AURKB is a serine/threonine kinase that regulates key events in mitosis, which makes it an attractive target for tailored anticancer therapy. Many reports have elaborated on the role of AURKB in neoplasia and cancer; however, no previous study has shown its role during organ development. Our previous experiments have highlighted the essential requirement for AURKB during adult exocrine regeneration. To investigate if AURKB is similarly required for progression during embryonic development, we pharmacologically inhibited AURKB in developing submandibular glands (SMGs) at embryonic day (E)13.5 and E16.5, using the highly potent and selective drug Barasertib. Inhibition of AURKB interfered with the expansion of the embryonic buds. Interestingly, this effect on SMG development was also seen when the mature explants (E16.5) were incubated for 24 h with another cell cycle inhibitor Aphidicolin. Barasertib prompted apoptosis, DNA damage and senescence, the markers of which (cleaved caspase 3, γH2AX, SA-βgal and p21, respectively), were predominantly seen in the developing buds. In addition to a reduction in cell cycling and proliferation of the epithelial cells in response to AURKB inhibition, Barasertib treatment led to an excessive generation of reactive oxygen species (ROS) that resulted in downregulation of the acinar differentiation marker Mist1. Importantly, inhibition of ROS was able to rescue this loss of identity, with Mist1 expression maintained despite loss of AURKB. Together, these data identify AURKB as a key molecule in supporting embryonic development and differentiation, while inhibiting senescence-inducing signals during organogenesis.

scholarly journals RNA-binding protein RNPC1 acts as an oncogene in gastric cancer by stabilizing Aurora kinase B mRNA

2021 ◽  
pp. 112741
Author(s):  
Chun-Mei Ji ◽  
Xu Zhang ◽  
Wentong Fang ◽  
Ling Meng ◽  
Xiaolong Wei ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Aurora Kinase ◽  
Aurora Kinase B
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