Adhesion of ST6Gal I-mediated human colon cancer cells to fibronectin contributes to cell survival by integrin beta1-mediated paxillin and AKT activation. 2010

Minyoung Lee, and Jung-Jin Park, and Yun-Sil Lee
Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Korea.

We have recently demonstrated that ionizing radiation (IR) of cells increased the expression of beta-galactoside alpha-(2,6)-sialyltransferase (ST6Gal I) and the level of glycoprotein sialylation, especially for the key adhesion molecule integrin beta1. In addition, ST6Gal I-mediated sialylation of integrin beta1 contributed to cell adhesion-mediated radioresistance in colon cancer cells. In this study, we examined IR-induced cell adhesion to the extracellular matrix and evaluated the role of integrin beta1-associated downstream signaling molecules, such as paxillin and AKT. IR exposure and ST6Gal I overexpression increased adhesion of SW480 colon cancer cells to fibronectin and contributed to cell survival through the activation of paxillin and AKT. In contrast, knockdown of ST6Gal I or paxillin reduced the level of radiation-induced cell adhesion and increased the level of cell death. These results suggest that integrin beta1 sialylation may play a critical role in promoting adhesion of cancer cells by integrin beta1-mediated paxillin and AKT activation.

UI MeSH Term Description Entries
D002448 Cell Adhesion Adherence of cells to surfaces or to other cells. Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D003110 Colonic Neoplasms Tumors or cancer of the COLON. Cancer of Colon,Colon Adenocarcinoma,Colon Cancer,Cancer of the Colon,Colon Neoplasms,Colonic Cancer,Neoplasms, Colonic,Adenocarcinoma, Colon,Adenocarcinomas, Colon,Cancer, Colon,Cancer, Colonic,Cancers, Colon,Cancers, Colonic,Colon Adenocarcinomas,Colon Cancers,Colon Neoplasm,Colonic Cancers,Colonic Neoplasm,Neoplasm, Colon,Neoplasm, Colonic,Neoplasms, Colon
D005353 Fibronectins Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. Cold-Insoluble Globulins,LETS Proteins,Fibronectin,Opsonic Glycoprotein,Opsonic alpha(2)SB Glycoprotein,alpha 2-Surface Binding Glycoprotein,Cold Insoluble Globulins,Globulins, Cold-Insoluble,Glycoprotein, Opsonic,Proteins, LETS,alpha 2 Surface Binding Glycoprotein
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000094802 beta-D-Galactoside alpha 2-6-Sialyltransferase Sialyltransferases that catalyze the transfer of N-ACETYLNEURAMINIC ACID from CYTIDINE MONOPHOSPHATE N-ACETYLNEURAMINIC ACID to the 6-OH of the GALACTOSE residue of N-GLYCANS. CMP-Acetylneuraminate Galactoside (alpha 2-6)-Sialyltransferase,CMP-N-Acetylneuraminate-Galactosylglycoprotein Sialyltransferase ST6GAL,CMP-N-Acetylneuraminate-beta-Galactoside alpha-2,6-Sialyltransferase,CMP-N-Acetylneuraminic Acid-Lactose Sialytransferase,CMP-NeuAc-Galactoside (alpha 2-6)-Sialyltransferase,CMP-Sialic Acid-N-Acetyllactosaminide alpha (2-6)-Sialyltransferase,Gal-1-4-GlcNAc alpha(2-6)-Sialyltransferase,alpha 2-6-Sialyltransferase,alpha2,6(N) Sialyltransferase,alpha6-Sialyltransferase,beta-D-Galactoside alpha-2-6-Sialyltransferase,beta-Galactoside alpha2,6-Sialyltransferase,beta-Galactosyl(1-4)N-Acetylglucosaminide alpha(2-6)-Sialyltransferase,Gal-GlcNAc(2-6)-sialyltransferase,SIAT-1,ST6(N),ST6Gal I,ST6Gal-1,2-6-Sialyltransferase, alpha,2-6-Sialyltransferase, beta-D-Galactoside alpha,Acid-Lactose Sialytransferase, CMP-N-Acetylneuraminic,CMP N Acetylneuraminate Galactosylglycoprotein Sialyltransferase ST6GAL,CMP N Acetylneuraminate beta Galactoside alpha 2,6 Sialyltransferase,CMP N Acetylneuraminic Acid Lactose Sialytransferase,SIAT 1,ST6GAL, CMP-N-Acetylneuraminate-Galactosylglycoprotein Sialyltransferase,ST6Gal 1,Sialyltransferase ST6GAL, CMP-N-Acetylneuraminate-Galactosylglycoprotein,Sialytransferase, CMP-N-Acetylneuraminic Acid-Lactose,alpha 2 6 Sialyltransferase,alpha 2-6-Sialyltransferase, beta-D-Galactoside,alpha-2,6-Sialyltransferase, CMP-N-Acetylneuraminate-beta-Galactoside,alpha-2-6-Sialyltransferase, beta-D-Galactoside,alpha2,6-Sialyltransferase, beta-Galactoside,alpha6 Sialyltransferase,beta D Galactoside alpha 2 6 Sialyltransferase,beta Galactoside alpha2,6 Sialyltransferase
D012799 Sialyltransferases A group of enzymes with the general activity CMP-N-acetylneuraminate:acceptor N-acetylneuraminyl transferase. They catalyze the transfer of N-ACETYLNEURAMINIC ACID from CMP-N-ACETYLNEURAMINIC ACID to an acceptor, which is usually the terminal sugar residue of an oligosaccharide, a glycoprotein, or a glycolipid. Glycoprotein Sialyltransferases,Glycosyltransferase Family 29,Sialyltransferase,Ectosialyltransferase,Glycoprotein Sialyltransferase,Sialyltransferase, Glycoprotein,Sialyltransferases, Glycoprotein
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D051057 Proto-Oncogene Proteins c-akt Protein-serine-threonine kinases that contain PLECKSTRIN HOMOLOGY DOMAINS and are activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. They play a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells. akt Proto-Oncogene Protein,c-akt Protein,AKT1 Protein Kinase,AKT2 Protein Kinase,AKT3 Protein Kinase,Akt-alpha Protein,Akt-beta Protein,Akt-gamma Protein,Protein Kinase B,Protein Kinase B alpha,Protein Kinase B beta,Protein Kinase B gamma,Protein-Serine-Threonine Kinase (Rac),Proto-Oncogene Protein Akt,Proto-Oncogene Protein RAC,Proto-Oncogene Proteins c-akt1,Proto-Oncogene Proteins c-akt2,Proto-Oncogene Proteins c-akt3,RAC-PK Protein,Rac Protein Kinase,Rac-PK alpha Protein,Rac-PK beta Protein,Related to A and C-Protein,c-akt Proto-Oncogene Protein,Akt alpha Protein,Akt beta Protein,Akt gamma Protein,Akt, Proto-Oncogene Protein,Protein, akt Proto-Oncogene,Protein, c-akt Proto-Oncogene,Proteins c-akt1, Proto-Oncogene,Proteins c-akt2, Proto-Oncogene,Proteins c-akt3, Proto-Oncogene,Proto Oncogene Protein Akt,Proto Oncogene Protein RAC,Proto Oncogene Proteins c akt,Proto Oncogene Proteins c akt1,Proto Oncogene Proteins c akt2,Proto Oncogene Proteins c akt3,Proto-Oncogene Protein, akt,Proto-Oncogene Protein, c-akt,RAC PK Protein,RAC, Proto-Oncogene Protein,Rac PK alpha Protein,Rac PK beta Protein,Related to A and C Protein,akt Proto Oncogene Protein,alpha Protein, Rac-PK,c akt Proto Oncogene Protein,c-akt, Proto-Oncogene Proteins,c-akt1, Proto-Oncogene Proteins,c-akt2, Proto-Oncogene Proteins,c-akt3, Proto-Oncogene Proteins
D051419 Paxillin Paxillin is a signal transducing adaptor protein that localizes to FOCAL ADHESIONS via its four LIM domains. It undergoes PHOSPHORYLATION in response to integrin-mediated CELL ADHESION, and interacts with a variety of proteins including VINCULIN; FOCAL ADHESION KINASE; PROTO-ONCOGENE PROTEIN PP60(C-SRC); and PROTO-ONCOGENE PROTEIN C-CRK.

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