title: Overexpression of αvβ6 integrin alters the colorectal cancer cell proteome in favor of elevated proliferation and a switching in cellular adhesion that increases invasion.
abstract: Many proteins enhance cancer progression toward life-threatening metastases. These include linking proteins called integrins that mediate cell adhesion to the extracellular matrix (ECM), consequently altering both function and phenotype. Specific neoexpression of the β6 integrin subunit correlates with the epithelial-to-mesenchymal transition, metastasis, and poor overall patient survival. While β6 is implicated in these processes, exactly how it affects signaling and/or proteolytic pathways in metastasis remains unclear. A membrane-enriched peptide immobilized pH gradient isoelectric focusing (IPG-IEF) shotgun proteomics study was undertaken in which subclones of the SW480 colorectal cancer cell line transfected with a vector inducing unregulated β6 integrin overexpression were compared with the "empty" mock vector control cell line. β6 overexpression induced a significant change in 708 proteins and was found to be localized across most intracellular locations, some involving cellular processes and pathways underpinning cancer progression. Proteomics data have been deposited to the ProteomeXchange with identifier PXD000230. β6 expression increased cell proliferation 4-fold while decreasing cell adhesion to many integrin ECM substrates. β6 expression also enhanced cell invasion and promoted the expression/repression of many established cancer-related pathways.
authors.affiliation: Department of Chemistry and Biomolecular Sciences and Australian Proteome Analysis Facility, Faculty of Science, Macquarie University, NSW 2109, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Cantor
authors.forename: Iveta
authors.initials: I
authors.lastname: Slapetova
authors.forename: Alison
authors.initials: A
authors.lastname: Kan
authors.forename: Leon R
authors.initials: LR
authors.lastname: McQuade
authors.forename: Mark S
authors.initials: MS
authors.lastname: Baker
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016023:Integrins / Q000235:genetics* / Q000378:metabolism; D007525:Isoelectric Focusing / Q000379:methods; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D025941:Protein Interaction Mapping; D020543:Proteome / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D016023:Integrins; D009363:Neoplasm Proteins; D020543:Proteome; C073878:integrin alphavbeta6