% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Collura:307455,
      author       = {J. L. Collura and K. C. Lei$^*$ and M. Chandra and T.
                      Kervarrec and H. J. Park and M. Dalkoohi and J. Becker$^*$
                      and Y. Chang and P. S. Moore and M. Shuda},
      title        = {{P}harmacologic reversion of {M}erkel cell carcinoma via
                      {CBP}/p300 inhibition.},
      journal      = {Proceedings of the National Academy of Sciences of the
                      United States of America},
      volume       = {122},
      number       = {52},
      issn         = {0027-8424},
      address      = {Washington, DC},
      publisher    = {National Acad. of Sciences},
      reportid     = {DKFZ-2025-03054},
      pages        = {e2516667122},
      year         = {2025},
      abstract     = {Merkel cell polyomavirus (MCV) T antigen functions as an
                      oncoprotein that drives the transformation of Merkel cell
                      carcinoma (MCC) cells by activating transcription factors
                      involved in cell proliferation. The viral T antigen promoter
                      requires the activity of the cellular coactivator
                      CREB-binding protein (CBP)/p300 for its expression.
                      Inhibition of CBP/p300 with two distinct small-molecule
                      inhibitors suppresses T antigen expression, leading to cell
                      cycle arrest and upregulation of the cell cycle inhibitor
                      p27Kip1. This shift promotes neuronal differentiation,
                      associated with neurite outgrowth in MCC cells. RNA
                      sequencing revealed downregulation of genes involved in E2F,
                      Myc, mTORC1 oncogenic signaling, as well as markers of the
                      Merkel cell lineage including Sox2 and Atoh1. Notably, a
                      rare MCC case exhibiting a mixed cellular composition, with
                      loss of T antigen expression and neuroblastic phenotype,
                      showed a transcriptomic profile resembling that of MCC cells
                      treated with CBP/p300 inhibitors. This suggests that similar
                      differentiation processes may contribute to tumor
                      heterogeneity in patients. This study presents the model
                      system enabling reversible switching between a transformed
                      and differentiated cell state in a human cancer using
                      small-molecule treatment.},
      keywords     = {Carcinoma, Merkel Cell: drug therapy / Carcinoma, Merkel
                      Cell: metabolism / Carcinoma, Merkel Cell: pathology /
                      Carcinoma, Merkel Cell: genetics / Carcinoma, Merkel Cell:
                      virology / Humans / Merkel cell polyomavirus: metabolism /
                      E1A-Associated p300 Protein: antagonists $\&$ inhibitors /
                      E1A-Associated p300 Protein: metabolism / CREB-Binding
                      Protein: antagonists $\&$ inhibitors / CREB-Binding Protein:
                      metabolism / Cell Line, Tumor / Gene Expression Regulation,
                      Neoplastic: drug effects / Skin Neoplasms: drug therapy /
                      Skin Neoplasms: metabolism / Skin Neoplasms: pathology /
                      Skin Neoplasms: genetics / Antigens, Viral, Tumor:
                      metabolism / Antigens, Viral, Tumor: genetics / Cell
                      Proliferation: drug effects / Cell Differentiation: drug
                      effects / p300-CBP Transcription Factors: antagonists $\&$
                      inhibitors / p300-CBP Transcription Factors: metabolism /
                      CBP/p300 (Other) / Merkel cell carcinoma (Other) / Merkel
                      cell polyomavirus (Other) / T antigen (Other) / cancer
                      reversion (Other) / E1A-Associated p300 Protein (NLM
                      Chemicals) / CREB-Binding Protein (NLM Chemicals) / EP300
                      protein, human (NLM Chemicals) / CREBBP protein, human (NLM
                      Chemicals) / Antigens, Viral, Tumor (NLM Chemicals) /
                      p300-CBP Transcription Factors (NLM Chemicals)},
      cin          = {ED01},
      ddc          = {500},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41439710},
      doi          = {10.1073/pnas.2516667122},
      url          = {https://inrepo02.dkfz.de/record/307455},
}