15-Lipoxygenase-1 expression suppresses the invasive properties of colorectal carcinoma cell lines HCT-116 and HT-29.
Colorectal carcinoma (CRC) is often lethal when invasion and/or metastasis occur. 15-Lipoxygenase-1 (15-LO-1), a member of the inflammatory eicosanoid pathway, oxidatively metabolizes linoleic acid and its expression is repressed in CRC. In this study, we investigated the hypothesis that the lack of 15-LO-1 expression in CRC cells might contribute to tumorigenesis. Therefore we introduced 15-LO-1 into HCT-116 and HT-29 cells that do not have detectable levels of 15-LO-1. Our data indicate that expression of 15-LO-1 significantly decreased cell proliferation and increased apoptosis. In addition, we observed a reduction in adhesion to fibronectin, anchorage-independent growth on soft agar, cellular motility and ability to heal a scratch wound, and migratory and invasive capacity across Matrigel. 15-LO-1 expression also reduced the expression of metastasis associated protein-1, a part of the nucleosome remodeling and histone deacetylase silencing complex. We propose that 15-LO-1 expression in CRC might contribute to the inhibition of metastatic capacity in vitro and can be exploited for therapeutic purposes.
Cimen
Ismail
I
Department of Biological Sciences, Middle East Technical University, Ankara, Turkey.
Tunçay
Seda
S
Banerjee
Sreeparna
S
D017209:Apoptosis; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000473:pathology*; D045325:HCT116 Cells; D006655:Histone Deacetylases / Q000502:physiology; D006801:Humans; D008041:Linoleic Acids / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012097:Repressor Proteins / Q000502:physiology; D015534:Trans-Activators
D008041:Linoleic Acids; C089320:MTA1 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; C024348:13-hydroxy-9,11-octadecadienoic acid; D001093:Arachidonate 15-Lipoxygenase; D006655:Histone Deacetylases