ライフサイエンスコーパス: AURKA

1 AURKA inhibitors may provide a therapeutic strategy for

2 AURKA inhibitors might be developed as therapeutic agent

3 AURKA upregulation by BMI1 exerts several effects, inclu

4 AURKA was found to regulate NF-kappaB activity by bindin

5 of FGFR4 (n = 6 [30%]), FLT1 (n = 4 [20%]), AURKA (n = 2 [10%]) and loss of ESR1 expression (n = 9 [

6 The essential mitotic kinase Aurora A (AURKA) is controlled during cell cycle progression via t

7 ng inhibitor of the mitotic kinase Aurora A (AURKA) with an MDM2 antagonist activates p53 in senescen

8 The Aurora kinases, which include Aurora A (AURKA), Aurora B (AURKB) and Aurora C (AURKC), are serin

9 cancer progression, interacts with Aurora-A (AURKA) kinase to control ciliary resorption, and with Sr

10 d associated with increased Aurora kinase A (AURKA) and histone deacetylase 6 (HDAC6) activities, whi

11 on of the mitotic regulator Aurora kinase A (AURKA) drives tumor aneuploidy and chromosomal instabili

12 entrosome-localized mitotic Aurora kinase A (AURKA) facilitates G2/M events.

13 The aurora kinase A (AURKA) gene is frequently amplified and overexpressed in

14 we reported a novel role of Aurora kinase A (AURKA) in BCSCs, as a transactivating co-factor in the i

15 We investigated the role of Aurora kinase A (AURKA) in regulating p73-dependent apoptosis using the p

16 We find that Aurora kinase A (AURKA) is a novel, hypoxia-independent target for VHL ub

17 Aurora kinase A (AURKA) is a therapeutic target in acute megakaryocytic l

18 Aurora kinase A (AURKA) is located at 20q13, a region that is frequently

19 ous analyses suggested that Aurora kinase A (AURKA) is regulated by androgens in prostate cancer cell

20 Aurora kinase A (AURKA) localizes to centrosomes and mitotic spindles whe

21 ic and genetic studies that aurora kinase A (AURKA) represents a new therapeutic target in PMF.

22 report that LKB1 undergoes Aurora kinase A (AURKA)-mediated phosphorylation, which largely compromis

23 t a major target of diMF is Aurora kinase A (AURKA).

24 response element, whereas FOXM1 can activate AURKA expression at the transcriptional level in a simil

25 In addition, AURKA/B inhibitors phenocopy the effects of BETi.

26 ble in myeloma cells, including AKT1, AK3L1, AURKA, AURKB, CDC2L1, CDK5R2, FES, FLT4, GAK, GRK6, HK1,

27 cells was also significantly inhibited by an AURKA specific inhibitor, alisertib (MLN8237).

28 ssemination and evaluated the efficacy of an AURKA-selective small molecule inhibitor, alisertib (MLN

29 r, we found that coamplification of BMI1 and AURKA correlated with poorer prognosis.

30 ra A levels increase in advanced disease and AURKA is an AR-V target gene demonstrating a positive fe

31 Moreover, both FOXM1 and AURKA were essential for maintaining the BCSC population

32 n between the expression levels of FOXM1 and AURKA.

33 d melanoma tumors to coadministered MDM2 and AURKA inhibitors offers a sound rationale for clinical e

34 A and decreased proliferation, and NANOG and AURKA expression are positively correlated in HNSCCs.

35 on therapy with NEDD9 short hairpin RNAs and AURKA inhibitors impairs tumor growth and distant metast

36 These functions nominate SRC and AURKA as valuable therapeutic targets for cancer, and in

37 ment and mitotic control, suggesting SRC and AURKA might interact directly.

38 SRC and AURKA share a common interaction partner, NEDD9, which s

39 mutual cross-phosphorylation between SRC and AURKA that enhanced SRC kinase activity.

40 al development of stem cells in AML, such as AURKA over-expression.

41 Two Aurora kinase isoforms, A and B (AURKA and AURKB), are expressed ubiquitously in mammals,

42 y the suppression of Aurora kinases A and B (AURKA/B), which are critical mediators of mitosis.

43 of CaM activity reduces interaction between AURKA and its activator, NEDD9.

44 ed positive feedback signalling loop between AURKA and FOXM1, crucial for BCSC self-renewal.

45 Blocking AURKA nuclear localization inhibits this newly discovere

46 lts link CSCs, EMT, and CIN through the BMI1-AURKA axis and suggest therapeutic use from inhibiting A

47 as a downstream target that was repressed by AURKA.

48 in mitosis when it localizes to centrosomes, AURKA is allosterically activated on the mitotic spindle

49 Clinically, AURKA displays high levels in NSCLC patients, and correl

50 point to the potential utility of combining AURKA inhibitors with taxanes as a therapeutic strategy

51 NEDD9 confers AURKA stability by limiting the binding of the cdh1-subs

52 acted synergistically to inhibit cytoplasmic AURKA activity and disrupt the nuclear AURKA/FOXM1-posit

53 Flash reporter activity, whereas kinase dead AURKA mutant (D274A) had no effect.

54 Indeed, kinase-dead AURKA can effectively transactivate the FOXM1 promoter t

55 ogenic property of the spatially deregulated AURKA in tumorigenesis and provide a potential therapeut

56 f the key spindle assembly regulators (i.e., AURKA, PLK1, and gamma-tubulin) to the microtubule-organ

57 nockdown activated beta-catenin and elevated AURKA expression, decreased primary cilia formation, and

58 By contrast, we found that elevated AURKA expression is not increased by HIF-1alpha, suggest

59 The siRNA knockdown of endogenous AURKA reversed these effects and Western blot analysis s

60 Binding of NEDD9 to AURKA is critical for AURKA stabilization, as mutation of S296E was sufficient

61 alpha, suggesting an alternate mechanism for AURKA dysregulation in VHL-null cells.

62 underscoring a novel oncogenic potential for AURKA in gastric tumorigenesis.

63 show that Ca(2+)/CaM binding is required for AURKA activation in mitosis and that inhibition of CaM a

64 ciated protein 5 (HURP/DLGAP5), required for AURKA-dependent, centrosome-independent mitotic spindle

65 together, these findings support a role for AURKA in EOC dissemination by regulating migration and a

66 urrent study, we identified a novel role for AURKA in regulating ovarian cancer cell dissemination an

67 noprecipitation with antibodies specific for AURKA and GSK-3beta indicated that the two proteins coex

68 n tissue samples, and mouse models, we found AURKA to be up-regulated during chronic inflammation to

69 patients, including SRC, SMAD family genes, AURKA, EGFR, HSP90, and PDGFR.

70 e elevated levels of AURKA protein, few have AURKA gene amplification, implying that posttranscriptio

71 CLC initiation and progression, highlighting AURKA as a potential therapeutic target for combatting h

72 The recombinant human AURKA protein phosphorylated the GSK-3beta protein at Se

73 herapeutic target for combatting hyperactive AURKA-driven NSCLCs.

74 We identify AURKA activity as essential in NSCLC cells lacking SMARC

75 These results implicate AURKA as an effective biomarker for bladder cancer detec

76 the Y- pocket induces structural changes in AURKA that inhibit catalytic activity in vitro and in ce

77 A decrease in AURKA, concomitant with increased ubiquitination and pro

78 activator of AURKA, is directly involved in AURKA stability.

79 o-fold increase in the proliferation rate in AURKA overexpressing cells.

80 FOSL1 targets include AURKA, whose inhibition impairs viability of mutant KRAS

81 atic activity of multiple kinases, including AURKA, FLT3, GSK3A, MAP3K, MEK, RSK2, RSK4, PLK4, ULK1,

82 r accumulation of beta-catenin and increased AURKA signaling to HDAC6.

83 actor-1alpha (HIF-1alpha) mediates increased AURKA expression in VHL-null cells.

84 rlying mechanism by which VHL loss increases AURKA levels has not been clearly elucidated, although i

85 Indeed, AURKA overexpression led to a significant increase in th

86 ere found to be responsible for BMI1-induced AURKA expression.

87 n unexpected structural mechanism to inhibit AURKA activity and mitotic localization.

88 Moreover, HIF-1alpha inhibited AURKA expression by inhibiting beta-catenin transcriptio

89 Instead, AURKA preferentially interacts with heterogeneous nuclea

90 ost mitotic cells express two AURK isoforms (AURKA and AURKB), mammalian germ cells also express a th

91 Aurora A kinase (AURKA) is overexpressed in 96% of human cancers and is c

92 The centrosomal Aurora-A kinase (AURKA) regulates mitotic progression, and overexpression

93 Among these, a role for basal body-localized AURKA in regulating ciliary disassembly in interphase ce

94 Mechanically, AURKA-mediated phosphorylation of LKB1 impairs LKB1 inte

95 hanism, cells exposed to AurkinA mislocalise AURKA from mitotic spindle microtubules.

96 kinases required for the control of mitosis (AURKA and AURKB) and meiosis (AURKC).

97 e as the target for a new class of dual-mode AURKA inhibitors, with implications for the chemical bio

98 r targeting both the cytoplasmic and nuclear AURKA function to effectively eliminate BCSCs, so as to

99 ction and transcriptional network of nuclear AURKA in BCSCs remain unknown.

100 Here, we report that nuclear AURKA can be recruited by Forkhead box subclass M1 (FOXM

101 asmic AURKA activity and disrupt the nuclear AURKA/FOXM1-positive feedback loop, respectively, result

102 ogically, the amplification or activation of AURKA-induced impairment of the LKB1/AMPK signaling path

103 re, we show that NEDD9, a known activator of AURKA, is directly involved in AURKA stability.

104 entified unexpected nonmitotic activities of AURKA.

105 The coexpression of AURKA together with TAp73 inhibited the activation of th

106 ence analysis demonstrated colocalization of AURKA and GSK-3beta proteins and a significant increase

107 Lastly, combination of AURKA and MEK inhibitors induces a deleterious effect on

108 ion in quiescent cells, where degradation of AURKA is required to maintain the primary cilium.

109 Finally, mutated derivatives of AURKA impaired for CaM binding and/or CaM-dependent acti

110 l lines were used to evaluate the effects of AURKA inhibition and overexpression on migration and adh

111 The effects of AURKA overexpression associated with poor clinical outco

112 d RNA interference to examine the effects of AURKA overexpression in human bladder cancer cells.

113 The expression of AURKA is increased upon androgen stimulation in LNCaP-AR

114 hese findings suggest that the expression of AURKA is regulated by androgen in prostate cancer cells

115 Conversely, enforced expression of AURKA resulted in increased migration, adhesion and acti

116 We correlated increased expression of AURKA with increased levels of tumor necrosis factor-alp

117 newly discovered transactivating function of AURKA, sensitizing resistant BCSC to kinase inhibition.

118 n, and overexpression and hyperactivation of AURKA commonly promotes genomic instability in many tumo

119 Inhibition of AURKA also reduced growth of xenograft tumors from human

120 mediated depletion or chemical inhibition of AURKA induces apoptosis and cell death in vitro and in x

121 l or RNA interference-mediated inhibition of AURKA significantly reduced ovarian carcinoma cell migra

122 LN8237 (Alisertib), a selective inhibitor of AURKA, induced polyploidization and expression of mature

123 tional small-molecule selective inhibitor of AURKA, reduced nuclear staining of nuclear factor-kappaB

124 The knockdown of AURKA reversed the phosphorylation of GSK-3beta and the

125 Cs, respectively) results in lower levels of AURKA and decreased proliferation, and NANOG and AURKA e

126 c mucosa of patients had increased levels of AURKA protein and nuclear NF-kappaB, compared with healt

127 e majority of tumors have elevated levels of AURKA protein, few have AURKA gene amplification, implyi

128 The mechanism of AURKA activation involves interactions with multiple par

129 resh insight into the catalytic mechanism of AURKA, and identify a key structural feature as the targ

130 Overexpression of AURKA and activation of its downstream pathway was enric

131 eta at Ser 9 following the overexpression of AURKA in AGS cells.

132 Overexpression of AURKA is common in cancer, resulting in acquisition of a

133 Overexpression of AURKA led to down-regulation of the TAp73-induced activa

134 induced AR binding in the intronic region of AURKA.

135 define Ca(2+)/CaM as important regulators of AURKA activation in mitotic and nonmitotic signaling.

136 this study, we have investigated the role of AURKA in regulating glycogen synthase kinase (GSK)-3beta

137 We investigated the roles of AURKA in inflammation and gastric tumorigenesis.

138 Although most studies of AURKA focus on its role in mitosis, some recent work ide

139 ur findings provide rationale for the use of AURKA inhibitors in treatment of metastatic tumors and p

140 beta-catenin levels in cells overexpressing AURKA.

141 , these findings demonstrate that LIN28B-RAN-AURKA signaling drives neuroblastoma oncogenesis, sugges

142 nsive transcription inhibitor iCRT14 reduced AURKA levels and rescued ciliary defects, inducing a sig

143 icient to disrupt binding and led to reduced AURKA protein levels.

144 define a role for beta-catenin in regulating AURKA and formation of primary cilia in the setting of V

145 at posttranscriptional mechanisms regulating AURKA protein levels are significant.

146 mplex-dependent mechanism, thereby relieving AURKA expression from let-7i suppression.

147 However, suppression of RNF4, AURKA, or PLK1 returned the reinitiation of replication

148 Treatment with MLN8237, a selective AURKA inhibitor, promoted polyploidization and different

149 RKA, in a PHD-independent reaction targeting AURKA for degradation in quiescent cells, where degradat

150 Here, we provide further evidence that AURKA is significantly overexpressed in AR-positive CRPC

151 We show here that AURKA activation at the basal body in ciliary disassembl

152 We report here that AURKA expression is driven by beta-catenin transcription

153 Taken together, our results indicate that AURKA regulates TAp73-dependent apoptosis and highlight

154 NMT promoter luciferase assays revealed that AURKA's effects on NNMT were caused by PAX3-mediated tra

155 In addition, we show that AURKA and FOXM1 participate in a tightly coupled positiv

156 Here we show that AURKA translocates to the nucleus and causes distinct on

157 The AURKA/MDM2 combination therapy shows adequate bioavailab

158 ed Tyr-Ser-Tyr motif from TPX2, blocking the AURKA-TPX2 interaction.

159 tic kinase Aurora A, which is encoded by the AURKA gene.

160 We also show that the FISH test for the AURKA gene copy number in urine yielded a specificity of

161 apoptosis and highlight the potential of the AURKA inhibitor MLN8054 in treating cancers that are def

162 -ubiquitin ligase RNF4 and activation of the AURKA-PLK1 pathway.

163 f AurkinA, a novel chemical inhibitor of the AURKA-TPX2 interaction, which acts via an unexpected str

164 Finally, we demonstrated that the AURKA inhibitor AKI603 and FOXM1 inhibitor thiostrepton

165 We conclude that the AURKA/GSK-3beta interaction is important in regulating b

166 gnition subunit of APC/C ubiquitin ligase to AURKA.

167 Binding of NEDD9 to AURKA is critical for AURKA stabilization, as mutation o

168 d predict the sensitivity of the patients to AURKA inhibitors based on NEDD9 expression.

169 EDD9 in tumor cells increases sensitivity to AURKA inhibitors.

170 ed additional targets including ZIC1, TOP2A, AURKA, and IGF-1R, which could form the basis of future

171 quitinate HIFalpha is unable to ubiquitinate AURKA.

172 y, VHL mono-, rather than poly-ubiquitinates AURKA, in a PHD-independent reaction targeting AURKA for

173 ivated the Akt pathway, thereby upregulating AURKA expression through activation of the beta-catenin/

174 fibrosis in PMF and that targeting them with AURKA inhibitors has the potential to provide therapeuti

175 Treatment with AURKA-selective small molecule inhibitor MLN8054 led to