ISG15 disrupts cytoskeletal architecture and promotes motility in human breast cancer cells

Shyamal D. Desai, Ryan E. Reed, Julian Burks, Laurence M. Wood, Ashok K. Pullikuth, Arthur L. Haas, Leroy-Fong Liu, Jerome W. Breslin, Sally Meiners, Surendran Sankar

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

Abstract

The interferon-stimulated gene 15 (ISG15) pathway is highly elevated in breast cancer; however, very little is known about how the ISG15 pathway contributes to breast tumorigenesis. In the current study, using the gene disruption approach, we demonstrate that both ISG15 and UbcH8 (ISG15-specific conjugating enzyme) disrupt F-actin architecture and formation of focal adhesions in ZR-75-1 breast cancer cells. In addition, ISG15 and UbcH8 promote breast cancer cell migration. We also demonstrate that ISG15 inhibits ubiquitin/26S proteasome-mediated turnover of proteins implicated in tumor cell motility, invasion and metastasis. Together, our results suggest that the aberrant activation of the ISG15 pathway confers a motile phenotype to breast cancer cells by disrupting cell architecture and stabilizing proteins involved in cell motility, invasion and metastasis. Because the cellular architecture is conserved and the ISG15 pathway is constitutively activated in tumor cells of different lineages, it is reasonable to assume that our observations in breast cancer must hold true for many other tumors.

Original languageEnglish
Pages (from-to)38-49
Number of pages12
JournalExperimental Biology and Medicine
Volume237
Issue number1
DOIs
Publication statusPublished - Jan 2012
Externally publishedYes

Keywords

  • Breast cancer
  • Cell architecture
  • Cell migration
  • Interferon
  • ISG15
  • Ubiquitin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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