title: Characterization of Laminin Binding Integrin Internalization in Prostate Cancer Cells.
abstract: Laminin binding integrins α6 (CD49f) and α3 (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, α6 integrin internalized with a rate constant (kactual) of 3.25 min-1, threefold faster than α3 integrin (1.0 min-1), 1.5-fold faster than the vitronectin binding αv integrin (CD51) (2.2 min-1), and significantly slower than the unrelated transferrin receptor (CD71) (15 min-1). Silencing of α3 integrin protein expression in DU145, PC3, and PC3B1 cells resulted in up to a 1.71-fold increase in kactualfor α6 integrin. The internalized α6 integrin was targeted to early endosomes but not to lamp1 vesicles. Depletion of α3 integrin expression resulted in redistribution of α6β4 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 α3 integrin increased cell migration by 1.8-fold, which was dependent on α6β1 integrin. Silencing of α6 integrin expression however, had no significant effect on the kactualof α3 integrin or its distribution in early endosomes. These results indicate that α3 and α6 integrins have significantly different internalization kinetics and that coordination exists between them for internalization. J. Cell. Biochem. 118: 1038-1049, 2017. © 2016 Wiley Periodicals, Inc.
authors: Cancer Biology Program, University of Arizona, Tucson, Arizona 85724.
authors: Lipsa
authors: L
authors: Das
authors: The University of Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724.
authors: Todd A
authors: TA
authors: Anderson
authors: The University of Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724.
authors: Jaime M C
authors: JM
authors: Gard
authors: Department of Pharmacology, University of Arizona, Tucson, Arizona 85724.
authors: Isis C
authors: IC
authors: Sroka
authors: Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85724.
authors: Stephanie R
authors: SR
authors: Strautman
authors: The University of Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724.|Department of Pathology, University of Arizona, Tucson, Arizona 85724.
authors: Raymond B
authors: RB
authors: Nagle
authors: University of Washington, Seattle, Washington 98195.
authors: Colm
authors: C
authors: Morrissey
authors: Cedars Sinai Medical Center, Los Angeles, California 90048.
authors: Beatrice S
authors: BS
authors: Knudsen
authors: The University of Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724.|Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85724.|Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona 85724.
authors: Anne E
authors: AE
authors: Cress
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D011992:Endosomes / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D039422:Integrin alpha3 / Q000235:genetics / Q000378:metabolism*; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport
chemical_list: C000599264:ITGA3 protein, human; C588002:ITGA6 protein, human; D039422:Integrin alpha3; D039503:Integrin alpha6
keywords: ENDOSOMES; INTEGRIN; INTERNALIZATION KINETICS; LAMININ; PROSTATE CANCER