USP33, a new player in lung cancer, mediates Slit-Robo signaling

Protein Cell. 2014 Sep;5(9):704-13. doi: 10.1007/s13238-014-0070-z. Epub 2014 Jul 2.

Abstract

Ubiquitin specific protease 33 (USP33) is a multifunctional protein regulating diverse cellular processes. The expression and role of USP33 in lung cancer remain unexplored. In this study, we show that USP33 is down-regulated in multiple cohorts of lung cancer patients and that low expression of USP33 is associated with poor prognosis. USP33 mediates Slit-Robo signaling in lung cancer cell migration. Downregulation of USP33 reduces the protein stability of Robo1 in lung cancer cells, providing a previously unknown mechanism for USP33 function in mediating Slit activity in lung cancer cells. Taken together, USP33 is a new player in lung cancer that regulates Slit-Robo signaling. Our data suggest that USP33 may be a candidate tumor suppressor for lung cancer with potential as a prognostic marker.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Cohort Studies
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Kaplan-Meier Estimate
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / metabolism*
  • Prognosis
  • RNA Interference
  • Receptors, Immunologic / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / metabolism*

Substances

  • Intercellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Receptors, Immunologic
  • roundabout protein
  • USP33 protein, human
  • Ubiquitin Thiolesterase
  • Slit homolog 2 protein