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Ectopic expression of Zmiz1 induces cutaneous squamous cell malignancies in a mouse model of cancer

Laura M Rogers1, Jesse D Riordan, Brian L Swick

  • 1Department of Anatomy and Cell Biology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.

The Journal of Investigative Dermatology
|February 22, 2013
PubMed

Insights

A truncated Zmiz1 transcript drives skin cancer development and is overexpressed in various human cancers, suggesting ZMIZ1’s broader oncogenic role in epithelial cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Cutaneous squamous cell carcinoma (SCC) is a prevalent cancer with poorly understood genetic drivers.
  • Zmiz1 was identified as a potential oncogene in nonmelanoma skin cancer via mutagenesis screening.

Purpose of the Study:

  • To investigate the role of Zmiz1 in skin cancer development.
  • To characterize a novel mouse model for invasive keratoacanthoma.
  • To explore ZMIZ1's potential role in other epithelial cancers.

Main Methods:

  • Transposon mutagenesis screen to identify candidate oncogenes.
  • Analysis of Zmiz1 transcript variants in human SCCs.
  • Development of a skin-specific mouse model expressing a truncated Zmiz1 transcript.
  • Protein stability assays.
  • Analysis of ZMIZ1 expression in human breast, ovarian, and colon cancers.

Main Results:

  • Mutations in Zmiz1 lead to a truncated transcript similar to an overexpressed endogenous isoform in human SCCs.
  • A novel mouse model rapidly develops invasive keratoacanthoma upon skin-specific expression of the truncated Zmiz1.
  • The alternative Zmiz1 isoform exhibits enhanced protein stability compared to the full-length version.
  • ZMIZ1 is overexpressed in human breast, ovarian, and colon cancers, in addition to SCCs.

Conclusions:

  • A truncated Zmiz1 transcript contributes to skin cancer initiation and progression.
  • Zmiz1 plays a significant role in the pathogenesis of invasive keratoacanthoma.
  • ZMIZ1 may function as a broader oncogene in multiple types of epithelial cancers.

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