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10.18632/oncotarget.7872

http://scihub22266oqcxt.onion/10.18632/oncotarget.7872
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C5008343!5008343 !26959111
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suck abstract from ncbi


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pmid26959111
      Oncotarget 2016 ; 7 (16 ): 22050-63
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  • Knock-down of Hdj2/DNAJA1 co-chaperone results in an unexpected burst of tumorigenicity of C6 glioblastoma cells #MMPMID26959111
  • Meshalkina DA ; Shevtsov MA ; Dobrodumov AV ; Komarova EY ; Voronkina IV ; Lazarev VF ; Margulis BA ; Guzhova IV
  • Oncotarget 2016[Apr]; 7 (16 ): 22050-63 PMID26959111 show ga
  • The chaperone system based on Hsp70 and proteins of the DnaJ family is known to protect tumor cells from a variety of cytotoxic factors, including anti-tumor therapy. To analyze whether this also functions in a highly malignant brain tumor, we knocked down the expression of Hsp70 (HSPA1A) and its two most abundant co-chaperones, Hdj1 (DNAJB1) and Hdj2 (DNAJA1) in a C6 rat glioblastoma cell line. As expected, tumor depletion of Hsp70 caused a substantial reduction in its growth rate and increased the survival of tumor-bearing animals, whereas the reduction of Hdj1 expression had no effect. Unexpectedly, a reduction in the expression of Hdj2 led to the enhanced aggressiveness of the C6 tumor, demonstrated by its rapid growth, metastasis formation and a 1.5-fold reduction in the lifespan of tumor-bearing animals. The in vitro reduction of Hdj2 expression reduced spheroid density and simultaneously enhanced the migration and invasion of C6 cells. At the molecular level, a knock-down of Hdj2 led to the relocation of N-cadherin and the enhanced activity of metalloproteinases 1, 2, 8 and 9, which are markers of highly malignant cancer cells. The changes in the actin cytoskeleton in Hdj2-depleted cells indicate that the protein is also important for prevention of the amoeboid-like transition of tumor cells. The results of this study uncover a completely new role for the Hdj2 co-chaperone in tumorigenicity and suggest that the protein is a potential drug target.
  • |Animals [MESH]
  • |Brain Neoplasms/*pathology [MESH]
  • |Cell Line, Tumor [MESH]
  • |Cell Movement/physiology [MESH]
  • |Cell Proliferation/physiology [MESH]
  • |Gene Knockdown Techniques [MESH]
  • |Glioblastoma/*pathology [MESH]
  • |HSP40 Heat-Shock Proteins/*metabolism [MESH]
  • |HSP70 Heat-Shock Proteins/metabolism [MESH]
  • |Male [MESH]
  • |Neoplasm Invasiveness/pathology [MESH]
  • |Rats [MESH]


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