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@ARTICLE{Huang:177255,
      author       = {Y. Huang and L. Qi and M. Kogiso and Y. Du and F. K. Braun
                      and H. Zhang and L. F. Huang and S. Xiao and W.-Y. Teo and
                      H. Lindsay and S. Zhao and P. Baxter and J. M. F. Su and A.
                      Adesina and J. Yang and S. Brabetz$^*$ and M. Kool$^*$ and
                      S. M. Pfister$^*$ and M. Chintagumpala and L. Perlaky and Z.
                      Wang and Y. Zhou and T.-K. Man and X.-N. Li},
      title        = {{S}patial {D}issection of {I}nvasive {F}ront from {T}umor
                      {M}ass {E}nables {D}iscovery of {N}ovel micro{RNA} {D}rivers
                      of {G}lioblastoma {I}nvasion.},
      journal      = {Advanced science},
      volume       = {8},
      number       = {23},
      issn         = {2198-3844},
      address      = {Weinheim},
      publisher    = {Wiley-VCH},
      reportid     = {DKFZ-2021-02389},
      pages        = {e2101923},
      year         = {2021},
      note         = {2021 Dec;8(23):e2101923},
      abstract     = {Diffuse invasion is the primary cause of treatment failure
                      of glioblastoma (GBM). Previous studies on GBM invasion have
                      long been forced to use the resected tumor mass cells. Here,
                      a strategy to reliably isolate matching pairs of invasive
                      (GBMINV ) and tumor core (GBMTC ) cells from the brains of 6
                      highly invasive patient-derived orthotopic models is
                      described. Direct comparison of these GBMINV and GBMTC cells
                      reveals a significantly elevated invasion capacity in GBMINV
                      cells, detects 23/768 miRNAs over-expressed in the GBMINV
                      cells (miRNAINV ) and 22/768 in the GBMTC cells (miRNATC ),
                      respectively. Silencing the top 3 miRNAsINV (miR-126,
                      miR-369-5p, miR-487b) successfully blocks invasion of GBMINV
                      cells in vitro and in mouse brains. Integrated analysis with
                      mRNA expression identifies miRNAINV target genes and
                      discovers KCNA1 as the sole common computational target gene
                      of which 3 inhibitors significantly suppress invasion in
                      vitro. Furthermore, in vivo treatment with 4-aminopyridine
                      (4-AP) effectively eliminates GBM invasion and significantly
                      prolongs animal survival times (P = 0.035). The results
                      highlight the power of spatial dissection of functionally
                      accurate GBMINV and GBMTC cells in identifying novel drivers
                      of GBM invasion and provide strong rationale to support the
                      use of biologically accurate starting materials in
                      understanding cancer invasion and metastasis.},
      keywords     = {4-aminopyridine (Other) / KCNA1 (Other) / glioblastoma
                      (Other) / miRNA (Other) / patient derived orthotopic
                      xenograft (Other)},
      cin          = {B062 / HD01},
      ddc          = {624},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34719887},
      doi          = {10.1002/advs.202101923},
      url          = {https://inrepo02.dkfz.de/record/177255},
}