title: Surface-bound galectin-4 regulates gene transcription and secretion of chemokines in human colorectal cancer cell lines.
abstract: One long-term complication of chronic intestinal inflammation is the development of colorectal cancer. However, the mechanisms linking inflammation to the colorectal tumorigenesis are poorly defined. Previously, we have demonstrated that galectin-4 is predominantly expressed in the luminal epithelia of the gastrointestinal tract, and its loss of expression plays a key role in the colorectal tumorigenesis. However, the mechanism by which galectin-4 regulates inflammation-induced tumorigenesis is unclear. Here, we show that galectin-4 secreted by the colorectal cancer cell lines was bound to the cell surface. Neutralization of surface-bound galectin-4 with anti-galectin-4 antibody resulted in increased cell proliferation with concomitant secretion of several chemokines into the extracellular medium. Neutralization of the surface-bound galectin-4 also resulted in the up-regulation of transcription of 29 genes, several of which are components of multiple inflammation signaling pathways. In an alternate experiment, binding of recombinant galectin-4 protein to cell surface of the galectin-4-negative colorectal cancer cells resulted in increased p27, and decreased cyclin D1 and c-Myc levels, leading to cell cycle arrest and apoptosis. Together, these data demonstrated that surface-bound galectin-4 is a dual function protein-down-regulating cell proliferation and chemokine secretion in galectin-4-expressing colorectal cancer cells on one hand and inducing apoptosis in galectin-4-negative colorectal cancer cells on the other hand.
authors.affiliation: Department of Pharmaceutical Sciences, Appalachian College of Pharmacy, Oakwood, VA, USA.
authors.forename: U Subrahmanyeswara
authors.initials: US
authors.lastname: Rao
authors.affiliation: Department of Pharmaceutical Sciences, Appalachian College of Pharmacy, Oakwood, VA, USA.
authors.forename: Prema S
authors.initials: PS
authors.lastname: Rao
mesh_terms: D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018925:Chemokines / Q000096:biosynthesis / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D019938:Cyclin D1 / Q000378:metabolism; D037541:Galectin 4 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007413:Intestinal Mucosa / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism
chemical_list: C530104:CCND1 protein, human; D018925:Chemokines; D037541:Galectin 4; C489427:MYC protein, human; D018809:Proliferating Cell Nuclear Antigen; D016271:Proto-Oncogene Proteins c-myc; C413374:p27 antigen; D019938:Cyclin D1
keywords: Galectins; cancer; chemokines; colorectal cancer; galectin-4; inflammation