Talin1 targeting potentiates anti-angiogenic therapy by attenuating invasion and stem-like features of glioblastoma multiforme

Wonyoung Kang, Sung Heon Kim, Hee Jin Cho, Jun Jin, Jeouyongwu Lee, Kyeung Min Joo, Do Hyun Nam

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Glioblastoma multiforme (GBM) possesses florid angiogenesis. However, the antiangiogenic agent, Bevacizumab, did not improve overall survival of GBM patients. For more durable anti-angiogenic treatment, we interrogated resistant mechanisms of GBM against Bevacizumab. Serial orthotopic transplantation of in vivo Bevacizumabtreated GBM cells provoked complete refractoriness to the anti-angiogenic treatment. These tumors were also highly enriched with malignant phenotypes such as invasiveness, epithelial to mesenchymal transition, and stem-like features. Through transcriptome analysis, we identified that Talin1 (TLN1) significantly increased in the refractory GBMs. Inhibition of TLN1 not only attenuated malignant characteristics of GBM cells but also reversed the resistance to the Bevacizumab treatment. These data implicate TLN1 as a novel therapeutic target for GBM to overcome resistance to anti angiogenic therapies.

Original languageEnglish
Pages (from-to)27239-27251
Number of pages13
JournalOncotarget
Volume6
Issue number29
DOIs
StatePublished - 2015

Keywords

  • Anti-angiogenic therapy
  • Bevacizumab-resistance
  • Glioblastoma multiforme
  • Patient derived xenograft models
  • Talin1

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