scholarly journals Oncogenic PKA signaling stabilizes MYC oncoproteins via an aurora kinase A-dependent mechanism

2021 ◽  
Author(s):  
Gary K. L. Chan ◽  
Samantha Maisel ◽  
Yeonjoo C. Hwang ◽  
Rebecca R. B. Wolber ◽  
Phuong Vu ◽  
...  
Keyword(s):  
Drug Targets ◽  
Human Cancer ◽  
Aurora Kinase ◽  
Genetic Alterations ◽  
Genetic Changes ◽  
Aurora Kinase A ◽  
Protein Levels ◽  
Cancer Models ◽  
Tumor Types ◽  
Kinase A

AbstractGenetic alterations that activate protein kinase A (PKA) signaling are found across many tumor types, but their downstream oncogenic mechanisms are poorly understood. We used global phosphoproteomics and kinome activity profiling to map the conserved signaling outputs driven by diverse genetic changes that activate PKA in human cancer, including melanoma and fibrolamellar carcinoma (FLC). We define two consensus networks of effectors downstream of PKA in cancer models. One is centered on RAS/MAPK components, and a second involves Aurora Kinase A (AURKA). We find that AURKA stabilizes c-MYC and n-MYC protein levels and expression programs in PKA-dependent tumor models, in part via a positive feedback loop mediated by the oncogenic kinase PIM2. This process can be suppressed by conformation-disrupting AURKA inhibitors such as CD-532. Our findings elucidate two independent mechanisms of PKA-driven tumor cell growth and offer insight into drug targets for study in FLC and other PKA-dependent malignancies.

1032 poster MLN8054, A NOVEL INHIBITOR OF AURORA KINASE A SENSITIZES ANDROGEN-RESISTANT PROSTATE CANCER MODELS TO RADIATION

2011 ◽  
Vol 99 ◽  
pp. S386
Author(s):  
L. Moretti ◽  
K. Niermann ◽  
S. Schleicher ◽  
K.W. Kim ◽  
P. Kopsombut ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Aurora Kinase ◽  
Aurora Kinase A ◽  
Cancer Models ◽  
Kinase A

scholarly journals Effects of Aurora kinase A on mouse decidualization via Stat3-plk1-cdk1 pathway

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Peng-Chao Wang ◽  
Si-Ting Chen ◽  
Zeng-Ming Yang
Keyword(s):  
Signaling Pathway ◽  
Aurora Kinase ◽  
Aurora A ◽  
Aurora Kinase A ◽  
Protein Levels ◽  
Decidual Cells ◽  
Implantation Sites ◽  
Kinase A

Abstract Background Decidualization is essential to the successful pregnancy in mice. The molecular mechanisms and effects of Aurora kinase A (Aurora A) remain poorly understood during pregnancy. This study is the first to investigate the expression and role of Aurora A during mouse decidualization. Methods Quantitative real time polymerase chain reaction, western blotting and in situ hybridization were used to determine the expression of Aurora A in mouse uteri. Aurora A activity was inhibited by Aurora A inhibitor to explore the role of Aurora A on decidualization via regulating the Aurora A/Stat3/Plk1/Cdk1 signaling pathway. Results Aurora A was strongly expressed at implantation sites compared with inter-implantation sites. Furthermore, Aurora A was also significantly increased in oil-induced deciduoma compared with control. Both Aurora A mRNA and protein were significantly increased under in vitro decidualization. Under in vitro decidualization, Prl8a2, a marker of mouse decidualization, was significantly decreased by TC-S 7010, an Aurora A inhibitor. Additionally, Prl8a2 was reduced by Stat3 inhibitor, Plk1 inhibitor and Cdk1 inhibitor, respectively. Moreover, the protein levels of p-Stat3, p-Plk1 and p-Cdk1 were suppressed by TC-S 7010. The protein levels of p-Stat3, p-Plk1 and p-Cdk1 were also suppressed by S3I-201, a Stat3 inhibitor). SBE 13 HCl (Plk1 inhibitor) could reduce the protein levels of p-Plk1 and p-Cdk1. Collectively, Aurora A could regulate Stat3/Plk1/Cdk1 signaling pathway. Conclusion Our study shows that Aurora A is expressed in decidual cells and should be important for mouse decidualization. Aurora A/Stat3/Plk1/Cdk1 signaling pathway may be involved in mouse decidualization.

Die Expression der Aurora Kinase A korreliert mit dem Wnt-Modulator RACGAP1 im Magenkarzinom

2015 ◽  
Vol 53 (08) ◽  
Author(s):  
J Bornschein ◽  
J Nielitz ◽  
I Drozdov ◽  
M Selgrad ◽  
T Wex ◽  
...  
Keyword(s):  
Aurora Kinase ◽  
Aurora Kinase A ◽  
Kinase A

scholarly journals Targeting Aurora kinase A and JAK2 prevents GVHD while maintaining Tregand antitumor CTL function

2017 ◽  
Vol 9 (372) ◽  
pp. eaai8269 ◽  
Author(s):  
Brian C. Betts ◽  
Anandharaman Veerapathran ◽  
Joseph Pidala ◽  
Hua Yang ◽  
Pedro Horna ◽  
...  
Keyword(s):  
Aurora Kinase ◽  
Aurora Kinase A ◽  
Kinase A

Inhibition of Aurora Kinase A enhances chemosensitivity of medulloblastoma cell lines

2010 ◽  
Vol 55 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Ayman El-Sheikh ◽  
Rong Fan ◽  
Diane Birks ◽  
Andrew Donson ◽  
Nicholas K Foreman ◽  
...  
Keyword(s):  
Cell Lines ◽  
Aurora Kinase ◽  
Aurora Kinase A ◽  
Medulloblastoma Cell ◽  
Kinase A ◽  
Medulloblastoma Cell Lines

scholarly journals Aurora Kinase A Drives MTOC Biogenesis but Does Not Trigger Resumption of Meiosis in Mouse Oocytes Matured In Vivo1

2012 ◽  
Vol 87 (4) ◽  
Author(s):  
Petr Solc ◽  
Vladimir Baran ◽  
Alexandra Mayer ◽  
Tereza Bohmova ◽  
Gabriela Panenkova-Havlova ◽  
...  
Keyword(s):  
Aurora Kinase ◽  
Aurora Kinase A ◽  
Mouse Oocytes ◽  
Kinase A
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