Talin1 targeting potentiates anti-angiogenic therapy by attenuating invasion and stem-like features of glioblastoma multiforme
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Wonyoung Kang1,3, Sung Heon Kim4, Hee Jin Cho2, Juyoun Jin1,3, Jeongwu Lee5, Kyeung Min Joo1,2,4, Do-Hyun Nam2,3
1Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea
2Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea
3Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
4Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Korea
5Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
Do-Hyun Nam, e-mail: firstname.lastname@example.org
Kyeung Min Joo, e-mail: email@example.com
Keywords: glioblastoma multiforme, anti-angiogenic therapy, bevacizumab-resistance, Talin1, patient derived xenograft models
Received: April 30, 2015 Accepted: August 07, 2015 Published: August 20, 2015
Glioblastoma multiforme (GBM) possesses florid angiogenesis. However, the anti-angiogenic 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 Bevacizumab-treated 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.
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