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Updated: Dec 24, 2025

Merkel Cell Polyomavirus Infection and Detection
13:45

Merkel Cell Polyomavirus Infection and Detection

Published on: February 7, 2019

10.3K

Merkel cell polyomavirus activates LSD1-mediated blockade of non-canonical BAF to regulate transformation and

Donglim Esther Park1,2, Jingwei Cheng2,3, John P McGrath4

  • 1Program in Virology, Graduate School of Arts and Sciences, Harvard University, Cambridge, MA, USA.

Nature Cell Biology
|April 15, 2020
PubMed

Insights

Merkel cell carcinoma (MCC) growth depends on LSD1, a protein targeted for inhibition. The non-canonical BAF complex antagonizes LSD1, suggesting a potential therapeutic strategy for this skin cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Virology

Background:

  • Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer linked to Merkel cell polyomavirus.
  • Viral T antigens drive MCC pathogenesis by altering host gene expression.

Purpose of the Study:

  • To elucidate the molecular mechanisms driving MCC proliferation.
  • To identify novel therapeutic targets for MCC treatment.

Main Methods:

  • Investigated the role of viral small T antigen in regulating gene expression.
  • Utilized CRISPR-Cas9 screening to identify genetic interactions.
  • Assessed the effects of LSD1 and BRD9 inhibition on MCC cell growth and gene expression.

Main Results:

  • Viral small T antigen complex activates LSD1 (KDM1A) expression, which represses the lineage transcription factor ATOH1.
  • LSD1 inhibition significantly reduces MCC tumor growth in vitro and in vivo.
  • A forward-genetics screen revealed an antagonistic relationship between LSD1 and the non-canonical BAF (ncBAF) chromatin remodeler.
  • BRD9 inhibition partially rescued gene expression and chromatin accessibility changes induced by LSD1 inhibition.

Conclusions:

  • MCC is mechanistically dependent on LSD1 for tumor growth.
  • LSD1 and ncBAF antagonistically regulate overlapping gene sets in MCC.
  • ncBAF complex exhibits tumor suppressor functions in MCC, presenting a potential therapeutic avenue.

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