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@ARTICLE{AntnGarca:212425,
      author       = {P. Antón-García and E. B. Haghighi and K. Rose and G.
                      Vladimirov and M. Börries$^*$ and A. Hecht},
      title        = {{TGF}β1-{I}nduced {EMT} in the {MCF}10{A} {M}ammary
                      {E}pithelial {C}ell {L}ine {M}odel {I}s {E}xecuted
                      {I}ndependently of {SNAIL}1 and {ZEB}1 but {R}elies on
                      {JUNB}-{C}oordinated {T}ranscriptional {R}egulation.},
      journal      = {Cancers},
      volume       = {15},
      number       = {2},
      issn         = {2072-6694},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2023-00144},
      pages        = {558},
      year         = {2023},
      abstract     = {Epithelial-mesenchymal transition (EMT) fosters cancer cell
                      invasion and metastasis, the main cause of cancer-related
                      mortality. Growing evidence that SNAIL and ZEB transcription
                      factors, typically portrayed as master regulators of EMT,
                      may be dispensable for this process, led us to
                      re-investigate its mechanistic underpinnings. For this, we
                      used an unbiased computational approach that integrated
                      time-resolved analyses of chromatin structure and
                      differential gene expression, to predict transcriptional
                      regulators of TGFβ1-inducible EMT in the MCF10A mammary
                      epithelial cell line model. Bioinformatic analyses indicated
                      comparatively minor contributions of SNAIL proteins and ZEB1
                      to TGFβ1-induced EMT, whereas the AP-1 subunit JUNB was
                      anticipated to have a much larger impact.
                      CRISPR/Cas9-mediated loss-of-function studies confirmed that
                      TGFβ1-induced EMT proceeded independently of SNAIL proteins
                      and ZEB1. In contrast, JUNB was necessary and sufficient for
                      EMT in MCF10A cells, but not in A549 lung cancer cells,
                      indicating cell-type-specificity of JUNB EMT-regulatory
                      capacity. Nonetheless, the JUNB-dependence of EMT-associated
                      transcriptional reprogramming in MCF10A cells allowed to
                      define a gene expression signature which was regulated by
                      TGFβ1 in diverse cellular backgrounds, showed positively
                      correlated expression with TGFβ signaling in multiple
                      cancer transcriptomes, and was predictive of patient
                      survival in several cancer types. Altogether, our findings
                      provide novel mechanistic insights into the
                      context-dependent control of TGFβ1-driven EMT and thereby
                      may lead to improved diagnostic and therapeutic options.},
      keywords     = {JUNB (Other) / SNAIL1 (Other) / TGFβ signaling (Other) /
                      ZEB1 (Other) / breast cancer (Other) / chromatin
                      accessibility (Other) / epithelial-mesenchymal transition
                      (Other) / invasion (Other) / metastasis (Other) /
                      transcriptional regulation (Other)},
      cin          = {FR01},
      ddc          = {610},
      cid          = {I:(DE-He78)FR01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36672507},
      pmc          = {pmc:PMC9856774},
      doi          = {10.3390/cancers15020558},
      url          = {https://inrepo02.dkfz.de/record/212425},
}