Expression and functional characterization of galectins in human colorectal cancer



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Galectins are a family of proteins defined by shared consensus amino acid sequence and affinity for β-galactose-containing oligosaccharides. These proteins have been associated with various biological processes, such as cell adhesion, proliferation, signaling, differentiation and apoptosis. Recently, galectins have gained increasing importance in the field of cancers; however, their expression or function in the development of colorectal cancer (CRC) remains unclear. Thus, a comprehensive analysis of key galectins in CRC was carried out and the results obtained constitute a part of this thesis. Briefly, the human colon biopsies and tissue microarrays containing a gradient of pathology were analyzed for galectins expression. Utilizing a variety of CRC cell lines and molecular biological procedures, the functions of different galectins including cell proliferation, migration, motility, cell cycle and apoptosis were characterized. Results presented in the foregoing chapters, in general, indicate that galectins, which are expressed in the normal crypt epithelia, were significantly down-regulated during CRC progression. All of these galectins negatively regulated various signaling pathways, leading to decreased cell proliferation, motility and migration, and induced cell cycle arrest. Notably, re-expression of galectins promoted apoptosis through activation of caspases and modulation of mitochondrial membrane potential. This study demonstrates that loss of galectins is a common and specific event in CRC. Through their ability to participate and down-regulate the functions of a variety of signaling pathways, galectins reveal themselves as key proteins in the development and progression of CRC. These findings demonstrate that galectins are important molecules with tumor suppressor like properties; therefore, their upregulation through pharmacological agents will prove to be valuable in the prevention and control of CRC.



Galectins, Colorectal cancer (CRC)