Characterization of Laminin Binding Integrin Internalization in Prostate Cancer Cells
Anderson, Todd A.
Gard, Jaime M.C.
Sroka, Isis C.
Strautman, Stephanie R.
Nagle, Raymond B.
Knudsen, Beatrice S.
Cress, Anne E.
AffiliationCancer Biology Program, University of Arizona
he University of Arizona Cancer Center, University of Arizona
Department of Pharmacology, University of Arizona, Tucson
Department of Molecular and Cellular Biology, University of Arizona
Department of Pathology, University of Arizona
Department of Cellular and Molecular Medicine, University of Arizona
MetadataShow full item record
CitationCharacterization of Laminin Binding Integrin Internalization in Prostate Cancer Cells 2017, 118 (5):1038 Journal of Cellular Biochemistry
JournalJournal of Cellular Biochemistry
Rights© 2016 Wiley Periodicals, Inc.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractLaminin binding integrins 6 (CD49f) and 3 (CD49c) are persistently but differentially expressed in prostate cancer (PCa). Integrin internalization is an important determinant of their cell surface expression and function. Using flow cytometry, and first order kinetic modeling, we quantitated the intrinsic internalization rates of integrin subunits in a single cycle of internalization. In PCa cell line DU145, 6 integrin internalized with a rate constant (k(actual)) of 3.25min(-1), threefold faster than 3 integrin (1.0min(-1)), 1.5-fold faster than the vitronectin binding v integrin (CD51) (2.2min(-1)), and significantly slower than the unrelated transferrin receptor (CD71) (15min(-1)). Silencing of 3 integrin protein expression in DU145, PC3, and PC3B1 cells resulted in up to a 1.71-fold increase in k(actual) for 6 integrin. The internalized 6 integrin was targeted to early endosomes but not to lamp1 vesicles. Depletion of 3 integrin expression resulted in redistribution of 64 integrin to an observed cell-cell staining pattern that is consistent with a suprabasal distribution observed in epidermis and early PIN lesions in PCa. Depletion of 3 integrin increased cell migration by 1.8-fold, which was dependent on 61 integrin. Silencing of 6 integrin expression however, had no significant effect on the k(actual) of 3 integrin or its distribution in early endosomes. These results indicate that 3 and 6 integrins have significantly different internalization kinetics and that coordination exists between them for internalization. J. Cell. Biochem. 118: 1038-1049, 2017.
Note12 month embargo; Accepted manuscript online: 10 August 2016
VersionFinal accepted manuscript
SponsorsNIH [R01 CA 159406, CA 23074, CA 09213]