Tight junction-associated signaling pathways modulate cell proliferation in uveal melanoma.
OBJECTIVE
To investigate the role of tight junction (TJ)-associated signaling pathways in the proliferation of uveal melanoma.


METHODS
Human uveal melanoma cell lines overexpressing the TJ molecule blood vessel epicardial substance (Bves) were generated. The effects of Bves overexpression on TJ protein expression, cell proliferation, and cell cycle distribution were quantified. In addition, localization and transcription activity of the TJ-associated protein ZO-1-associated nucleic acid binding protein (ZONAB) were evaluated using immunofluorescence and bioluminescence reporter assays to study the involvement of Bves signaling in cell proliferation-associated pathways.


RESULTS
Bves overexpression in uveal melanoma cell lines resulted in increased expression of the TJ proteins occludin and ZO-1, reduced cell proliferation, and increased sequestration of ZONAB at TJs and reduced ZONAB transcriptional activity.


CONCLUSIONS
TJ proteins are present in uveal melanoma, and TJ-associated signaling pathways modulate cell signaling pathways relevant to proliferation in uveal melanoma.
Jayagopal
Ashwath
A
Department of Chemistry, Vanderbilt University, 7330 Stevenson Center, Nashville, TN 351822, USA. ash.jayagopal@vanderbilt.edu
Yang
Jin-Long
JL
Haselton
Frederick R
FR
Chang
Min S
MS
D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D005822:Genetic Vectors; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D019108:Tight Junctions / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014604:Uveal Neoplasms / Q000378:metabolism / Q000473:pathology*; D062826:Zonula Occludens-1 Protein
D022762:CCAAT-Enhancer-Binding Proteins; D015815:Cell Adhesion Molecules; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D062793:Occludin; D010750:Phosphoproteins; D014157:Transcription Factors; D062826:Zonula Occludens-1 Protein; C530749:POPDC1 protein, human; C568985:OCLN protein, human; C569042:TJP1 protein, human; C094867:YBX3 protein, human