title: Trop-2 is up-regulated in invasive prostate cancer and displaces FAK from focal contacts.
abstract: In this study, we show that the transmembrane glycoprotein Trop-2 is up-regulated in human prostate cancer (PCa) with extracapsular extension (stages pT3/pT4) as compared to organ-confined (stage pT2) PCa. Consistent with this evidence, Trop-2 expression is found to be increased in metastatic prostate tumors of Transgenic Adenocarcinoma of Mouse Prostate mice and to strongly correlate with α5β1 integrin levels. Using PCa cells, we show that Trop-2 specifically associates with the α5 integrin subunit, as binding to α3 is not observed, and that Trop-2 displaces focal adhesion kinase from focal contacts. In support of the role of Trop-2 as a promoter of PCa metastatic phenotype, we observe high expression of this molecule in exosomes purified from Trop-2-positive PCa cells. These vesicles are then found to promote migration of Trop-2-negative PCa cells on fibronectin, an α5β1 integrin/focal adhesion kinase substrate, thus suggesting that the biological function of Trop-2 may be propagated to recipient cells. In summary, our findings show that Trop-2 promotes an α5β1 integrin-dependent pro-metastatic signaling pathway in PCa cells and that the altered expression of Trop-2 may be utilized for early identification of capsule-invading PCa.
authors.affiliation: Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA.|Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.|Current address: Ce.S.I. - University of Chieti-Pescara, Chieti Scalo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Trerotola
authors.affiliation: Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA.|Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Kirat K
authors.initials: KK
authors.lastname: Ganguly
authors.affiliation: The Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ladan
authors.initials: L
authors.lastname: Fazli
authors.affiliation: Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA.|Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Carmine
authors.initials: C
authors.lastname: Fedele
authors.affiliation: Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA.|Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Huimin
authors.initials: H
authors.lastname: Lu
authors.affiliation: Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA.|Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Anindita
authors.initials: A
authors.lastname: Dutta
authors.affiliation: Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA.|Tumor Microenvironment and Metastasis Program, The Wistar Institute Cancer Center, Philadelphia, PA, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA.|Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Tiziana
authors.initials: T
authors.lastname: De Angelis
authors.affiliation: Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA.|Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Luke W
authors.initials: LW
authors.lastname: Riddell
authors.affiliation: Department of Biochemistry, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Riobo
authors.affiliation: The Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gleave
authors.affiliation: The Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Amina
authors.initials: A
authors.lastname: Zoubeidi
authors.affiliation: Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Pestell
authors.affiliation: Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA.|Tumor Microenvironment and Metastasis Program, The Wistar Institute Cancer Center, Philadelphia, PA, USA.
authors.forename: Dario C
authors.initials: DC
authors.lastname: Altieri
authors.affiliation: Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA.|Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Lucia R
authors.initials: LR
authors.lastname: Languino
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499380:TACSTD2 protein, human; C544766:TROP2 protein, mouse; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: TRAMP; exosome; gleason grade; metastasis; pT2/pT3/pT4 prostate cancer