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

作者: Wonyoung Kang , Sung Heon Kim , Hee Jin Cho , Juyoun Jin , Jeongwu Lee

DOI: 10.18632/ONCOTARGET.4835

关键词: PathologyCancer researchPhenotypeStem cellBevacizumabAngiogenesisGene expression profilingIn vivoTranscriptomeMedicineEpithelial–mesenchymal transition

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

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