title: In PC3 prostate cancer cells ephrin receptors crosstalk to β1-integrins to strengthen adhesion to collagen type I.
abstract: Eph receptor (Eph) and ephrin signaling can play central roles in prostate cancer and other cancer types. Exposed to ephrin-A1 PC3 prostate cancer cells alter adhesion to extracellular matrix (ECM) proteins. However, whether PC3 cells increase or reduce adhesion, and by which mechanisms they change adhesion to the ECM remains to be characterized. Here, we assay how ephrin-A1 stimulates PC3 cells to adhere to ECM proteins using single-cell force spectroscopy. We find that PC3 cells binding to immobilized ephrin-A1 but not to solubilized ephrin-A1 specifically strengthen adhesion to collagen I. This Eph-ephrin-A1 signaling, which we suppose is based on mechanotransduction, stimulates β1-subunit containing integrin adhesion via the protein kinase Akt and the guanine nucleotide-exchange factor cytohesin. Inhibiting the small GTPases, Rap1 or Rac1, generally lowered adhesion of PC3 prostate cancer cells. Our finding suggests a mechanism by which PC3 prostate cancer cells exposed to ephrins crosstalk to β1-integrins and preferably metastasize in bone, a collagen I rich tissue.
authors: 1] Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland [2] Center for Precision Engineering, Harbin Institute of Technology, Harbin 150001, China.
authors: Miao
authors: M
authors: Yu
authors: Center for Precision Engineering, Harbin Institute of Technology, Harbin 150001, China.
authors: Jinghe
authors: J
authors: Wang
authors: Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland.
authors: Daniel J
authors: DJ
authors: Muller
authors: Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland.
authors: Jonne
authors: J
authors: Helenius
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002450:Cell Communication; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000737:chemistry* / Q000378:metabolism; D036382:Ephrin-A1 / Q000737:chemistry / Q000494:pharmacology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry; D019012:Integrin beta1 / Q000378:metabolism*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D051379:Mice; D018625:Microscopy, Atomic Force; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D036081:Receptors, Eph Family / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D020827:rap1 GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D036382:Ephrin-A1; D055767:Immobilized Proteins; D019012:Integrin beta1; D036081:Receptors, Eph Family; D020830:rac1 GTP-Binding Protein; D020827:rap1 GTP-Binding Proteins
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