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Michalak, Malwina; Warnken, Uwe; André, Sabine; Schnölzer, Martina; Gabius, Hans-Joachim; Kopitz, Juergen (2016): Detection of Proteome Changes in Human Colon Cancer Induced by Cell Surface Binding of Growth-Inhibitory Human Galectin-4 Using Quantitative SILAC-Based Proteomics. In: Journal of Proteome Research, Vol. 15, No. 12: pp. 4412-4422
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Abstract

Endogenous lectins have the capacity to translate glycan-encoded information on the cell surface into effects on cell growth. As test cases to examine changes in protein presence associated with tumor growth inhibition, we applied SILAC-based proteomics on human colon carcinoma cells treated with galectin-4 (Gal-4). The five tested lines-LS 180, Vaco 432, Colo 205, CX 1, and HCT 116 responded with differentiation and reduced proliferation to Gal-4 binding. In proteomic analysis (mass spectral data deposited with PRIDE, PXD003489), 2654 proteins were quantified, of which 190 were down-regulated and 115 were up-regulated (>2-fold). 1D annotation analysis of the results indicated down-regulation of DNA replication-associated processes, while protein presence for secretory and transport functions appeared increased. The strongest induction was found for CALB2 (calretinin;similar to 24-fold), TGM2 (protein-glutamine gamma-glutamyltransferase 2;,similar to 11-fold), S100A3 (similar to 10-fold), and GSN (gelsolin;9.5-fold), and the most pronounced decreases were seen for CDKN2A (tumor suppressor ARF;similar to 6-fold), EPCAM (epithelial cell adhesion molecule;similar to 6-fold), UBE2C (ubiquitin-conjugating enzyme E2 C;similar to 5-fold), KIF2C (kinesin-like protein KIF2C;5-fold), and LMNB1 (lamin-B1;,similar to 5-fold). The presence of the common proliferation marker Ki-67 was diminished about 4-fold. By tracing significant alterations of protein expression likely relevant for the observed phenotypic effects, the capacity of a galectin to affect the proteome of human colon cancer cells at multiple sites is revealed.