title: Detection of Proteome Changes in Human Colon Cancer Induced by Cell Surface Binding of Growth-Inhibitory Human Galectin-4 Using Quantitative SILAC-Based Proteomics.
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; ∼24-fold), TGM2 (protein-glutamine γ-glutamyltransferase 2; ∼11-fold), S100A3 (∼10-fold), and GSN (gelsolin; 9.5-fold), and the most pronounced decreases were seen for CDKN2A (tumor suppressor ARF; ∼6-fold), EPCAM (epithelial cell adhesion molecule; ∼6-fold), UBE2C (ubiquitin-conjugating enzyme E2 C; ∼5-fold), KIF2C (kinesin-like protein KIF2C; 5-fold), and LMNB1 (lamin-B1; ∼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.
authors: Department of Applied Tumor Biology, Institute of Pathology, Medical School of the Ruprecht-Karls-University , 69120 Heidelberg, Germany.|Cancer Early Detection, German Cancer Research Center (DKFZ) , 69120 Heidelberg, Germany.
authors: Malwina
authors: M
authors: Michalak
authors: Functional Proteome Analysis, German Cancer Research Center (DKFZ) , 69120 Heidelberg, Germany.
authors: Uwe
authors: U
authors: Warnken
authors: Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich , Veterinärstraße 13, 80539 Munich, Germany.
authors: Sabine
authors: S
authors: André
authors: Functional Proteome Analysis, German Cancer Research Center (DKFZ) , 69120 Heidelberg, Germany.
authors: Martina
authors: M
authors: Schnölzer
authors: Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich , Veterinärstraße 13, 80539 Munich, Germany.
authors: Hans-Joachim
authors: HJ
authors: Gabius
authors: Department of Applied Tumor Biology, Institute of Pathology, Medical School of the Ruprecht-Karls-University , 69120 Heidelberg, Germany.|Cancer Early Detection, German Cancer Research Center (DKFZ) , 69120 Heidelberg, Germany.
authors: Juergen
authors: J
authors: Kopitz
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D037541:Galectin 4 / Q000378:metabolism / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D013058:Mass Spectrometry; D020543:Proteome / Q000032:analysis / Q000187:drug effects*; D040901:Proteomics / Q000379:methods
chemical_list: D037541:Galectin 4; D020543:Proteome
keywords: SILAC; adhesion; cancer; lectin; malignancy; proliferation