VHL loss predicts response to Aurora kinase A inhibitor in renal cell carcinoma cells

Molecular Medicine Reports
Xiao-Fei DingYing-Liang Wu

Abstract

The majority of molecular targets of anticancer agents are limited to a subset of patients, and therefore identification of more specific biomarkers that can be used to improve clinical outcomes is of increasing interest. The present study showed that von Hippel‑Lindau tumor suppressor (VHL) tumor‑suppressor activity may influence the therapeutic response to Aurora kinase A (AURKA) inhibitors in human renal cell carcinoma (RCC). VHL protein (pVHL) expression was evaluated by immunoblotting in the human RCC cell lines CAKI, ACHN, 786‑O, 769‑P and A498. The anti‑tumor activities of alisertib, an AURKA‑specific chemical inhibitor, were detected by Cell Counting Kit‑8 assay in vitro and mouse xenograft model in vivo. Additionally, the VHL‑mediated anti‑tumor activity was assessed in 769‑P and CAKI cells via the loss or gain of VHL. The results revealed that VHL‑deficient 786‑O, 769‑P and A498 cells were sensitive to alisertib. By contrast, alisertib‑resistant CAKI and ACHN cells expressed the wild type VHL gene. In addition, rescue or knockdown of VHL was observed to increase or decrease alisertib anti‑proliferation activity, respectively, in RCC cells. The inverse correlation between the VHL gene expression profile and alisertib s...Continue Reading

References

Mar 14, 2007·Urologic Oncology·Toshifumi KurahashiMasato Fujisawa
Dec 9, 2008·European Journal of Obstetrics, Gynecology, and Reproductive Biology·Nae-Fang TwuYi-Jen Chen
Feb 4, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tai-Lung ChaPei-Wen Hsiao
Jun 27, 2009·Cell Cycle·Frank EckerdtJames L Maller
Mar 3, 2010·Medicinal Research Reviews·Dhanasekaran KarthigeyanTapas K Kundu
Sep 25, 2010·Journal of the American Society of Nephrology : JASN·Jianyong XuMiguel A Esteban
Dec 24, 2014·Nature Reviews. Cancer·Lucy GossageEamonn R Maher
Feb 17, 2017·Biochemical Society Transactions·Vladislav KorobeynikovErica A Golemis
Jul 12, 2017·Nature Reviews. Nephrology·Edwin M PosadasRobert A Figlin
Sep 18, 2017·European Journal of Medicinal Chemistry·Ankit C Borisa, Hardik G Bhatt
Oct 11, 2017·Cancer Treatment Reviews·Francesco MassariDaniel Y C Heng
Oct 28, 2017·The Journal of Cell Biology·Yuejia HuangYixian Zheng

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