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
-
Roundabout Proteins
-
Signal Transduction / genetics
-
Signal Transduction / physiology*
-
Ubiquitin Thiolesterase / genetics
-
Ubiquitin Thiolesterase / metabolism*
Substances
-
Intercellular Signaling Peptides and Proteins
-
Nerve Tissue Proteins
-
Receptors, Immunologic
-
USP33 protein, human
-
Ubiquitin Thiolesterase
-
Slit homolog 2 protein