Talin1 targeting potentiates anti-angiogenic therapy by attenuating invasion and stem-like features of glioblastoma multiforme.
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.
Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Wonyoung
W
Kang
Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Korea.
Sung Heon
SH
Kim
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
Hee Jin
HJ
Cho
Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Juyoun
J
Jin
Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Jeongwu
J
Lee
Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.|Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Korea.
Kyeung Min
KM
Joo
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Do-Hyun
DH
Nam
D020533:Angiogenesis Inhibitors / Q000737:chemistry; D000818:Animals; D000068258:Bevacizumab / Q000737:chemistry; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology*; D016608:Talin / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; C518832:TLN1 protein, human; D016608:Talin; C496077:Tln1 protein, mouse; D000068258:Bevacizumab
Talin1; anti-angiogenic therapy; bevacizumab-resistance; glioblastoma multiforme; patient derived xenograft models