Overexpression of αvβ6 Integrin Alters
the Colorectal Cancer Cell Proteome in Favor of Elevated Proliferation
and a Switching in Cellular Adhesion That Increases Invasion
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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