Aurora A kinase and its activator TPX2 are potential therapeutic targets in KRAS-induced pancreatic cancer


Publication type
Article
Access rights
Open Access
Appears in Collections:
Metrics
Abstract
Purpose Oncogenic KRAS mutations are found in over 90% of pancreatic ductal adenocarcinomas (PDACs). As yet, however, no effective therapies are available for KRAS-induced malignancies. Therefore, research aimed at the identification of KRAS targets with therapeutic potential is warranted. Our goal was to investigate Aurora A (AURKA) and targeting protein for Xklp2 (TPX2) as potential therapeutic targets in PDAC. Methods AURKA and TPX2 expression was assessed using RNAseq and qRT-PCR in PDAC patient samples and matched nontumor pancreatic tissues. Publicly available PDAC datasets were used to investigate associations of AURKA and TPX2 expression levels with patient survival and the presence of KRAS mutations. Next, we used an Aurora kinase inhibitor, or KRAS, AURKA and TPX2 targeting using RNA interference in KRAS-mutant PDAC cells and, subsequently, analyzed their clonogenic and anchorage-independent growth and migration. Results We found that relative to matched non-tumor tissues, PDAC tumors displayed significantly higher expression levels of AURKA and TPX2. In addition, we found that AURKA and TPX2 were co-expressed in PDAC datasets, and that high expression levels of AURKA and TPX2 were associated with a shorter patient survival and with the presence of oncogenic KRAS mutations. In addition, we found that siRNA-mediated KRAS targeting in KRAS-mutant PDAC cells reduced AURKA and TPX2 expression. Furthermore, targeting AURKA or TPX2 in KRAS-mutant PDAC cells reduced their clonogenic and anchorage-independent growth, as well their migration. Conclusions From our data we conclude that AURKA and TPX2 may act as KRAS biomarkers in PDAC that can predict a worse prognosis, and that AURKA or TPX2 targeting in PDAC cells may reduce their transformed phenotype. These results indicate that AURKA and TPX2 may serve as promising targets to be explored for KRAS-mutant PDAC therapy.
Reference
Gomes-Filho SM, Santos EO, Bertoldi ERM, Scalabrini LC, Heidrich V, Dazzani B, et al. Aurora A kinase and its activator TPX2 are potential therapeutic targets in KRAS-induced pancreatic cancer. Cell. Oncol.. 2020 mar.. doi:10.1007/s13402-020-00498-5.
Link to cite this reference
https://repositorio.butantan.gov.br/handle/butantan/2998
Journal title
Issue Date
2020


Files in This Item:

Existing users please Login
10.1007s13402-020-00498-5.pdf
Size: 6.67 MB
Format: Adobe PDF
Embargoed until January 1, 2999    Request a copy
Show full item record

The access to the publications deposited in this repository respects the licenses from journals and publishers.