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Title: Stroma-induced Jagged1 expression drives PC3 prostate cancer cell migration; disparate effects of RIP-generated proteolytic fragments on cell behaviour and Notch signaling

Abstract

The Notch ligand Jagged1 is subject to regulated intramembrane proteolysis (RIP) which yields a soluble ectodomain (sJag) and a soluble Jagged1 intracellular domain (JICD). The full-length Jagged1 protein enhances prostate cancer (PCa) cell proliferation and is highly expressed in metastatic cells. However, little is known regarding the mechanisms by which Jagged1 or its RIP-generated fragments might promote PCa bone metastasis. In the current study we show that bone marrow stroma (BMS) induces Jagged1 expression in bone metastatic prostate cancer PC3 cells and that this enhanced expression is mechanistically linked to the promotion of cell migration. We also show that RIP-generated Jagged1 fragments exert disparate effects on PC3 cell behaviour and Notch signaling. In conclusion, the expression of both the full-length ligand and its RIP-generated fragments must be considered in tandem when attempting to regulate Jagged1 as a possible PCa therapy. - Highlights: • Bone marrow stroma induces Jagged1 expression in prostate cancer (PCa) PC3 cells. • This enhanced expression of full-length Jagged1 is required for PC3 cell migration. • Proteolytic fragments of Jagged1 exert disparate effects on PC3 cell behaviour. • Effects of fragments on cell behaviour do not correlate with Notch signaling. • Effects of Jagged1 and its fragmentsmore » on PCa metastasis likely to be complex.« less

Authors:
 [1];  [2];  [2];  [2];  [1]
  1. Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YQ (United Kingdom)
  2. Genito Urinary Cancer Research Group, Institute of Cancer Sciences, Paterson Building, The University of Manchester, Manchester Academic Health Science Centre, Wilmslow Road, Manchester, M20 4BX (United Kingdom)
Publication Date:
OSTI Identifier:
22596312
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 472; Journal Issue: 1; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BEHAVIOR; BONE MARROW; CELL PROLIFERATION; LIGANDS; METASTASES; NEOPLASMS; PROSTATE; PROTEINS; PROTEOLYSIS; SKELETON; THERAPY

Citation Formats

Delury, Craig, E-mail: c.delury@lancaster.ac.uk, Hart, Claire, E-mail: claire.hart@manchester.ac.uk, Brown, Mick, E-mail: michael.brown@ics.manchester.ac.uk, Clarke, Noel, E-mail: noel.clarke@christie.nhs.uk, and Parkin, Edward, E-mail: e.parkin@lancaster.ac.uk. Stroma-induced Jagged1 expression drives PC3 prostate cancer cell migration; disparate effects of RIP-generated proteolytic fragments on cell behaviour and Notch signaling. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2016.02.101.
Delury, Craig, E-mail: c.delury@lancaster.ac.uk, Hart, Claire, E-mail: claire.hart@manchester.ac.uk, Brown, Mick, E-mail: michael.brown@ics.manchester.ac.uk, Clarke, Noel, E-mail: noel.clarke@christie.nhs.uk, & Parkin, Edward, E-mail: e.parkin@lancaster.ac.uk. Stroma-induced Jagged1 expression drives PC3 prostate cancer cell migration; disparate effects of RIP-generated proteolytic fragments on cell behaviour and Notch signaling. United States. doi:10.1016/J.BBRC.2016.02.101.
Delury, Craig, E-mail: c.delury@lancaster.ac.uk, Hart, Claire, E-mail: claire.hart@manchester.ac.uk, Brown, Mick, E-mail: michael.brown@ics.manchester.ac.uk, Clarke, Noel, E-mail: noel.clarke@christie.nhs.uk, and Parkin, Edward, E-mail: e.parkin@lancaster.ac.uk. Fri . "Stroma-induced Jagged1 expression drives PC3 prostate cancer cell migration; disparate effects of RIP-generated proteolytic fragments on cell behaviour and Notch signaling". United States. doi:10.1016/J.BBRC.2016.02.101.
@article{osti_22596312,
title = {Stroma-induced Jagged1 expression drives PC3 prostate cancer cell migration; disparate effects of RIP-generated proteolytic fragments on cell behaviour and Notch signaling},
author = {Delury, Craig, E-mail: c.delury@lancaster.ac.uk and Hart, Claire, E-mail: claire.hart@manchester.ac.uk and Brown, Mick, E-mail: michael.brown@ics.manchester.ac.uk and Clarke, Noel, E-mail: noel.clarke@christie.nhs.uk and Parkin, Edward, E-mail: e.parkin@lancaster.ac.uk},
abstractNote = {The Notch ligand Jagged1 is subject to regulated intramembrane proteolysis (RIP) which yields a soluble ectodomain (sJag) and a soluble Jagged1 intracellular domain (JICD). The full-length Jagged1 protein enhances prostate cancer (PCa) cell proliferation and is highly expressed in metastatic cells. However, little is known regarding the mechanisms by which Jagged1 or its RIP-generated fragments might promote PCa bone metastasis. In the current study we show that bone marrow stroma (BMS) induces Jagged1 expression in bone metastatic prostate cancer PC3 cells and that this enhanced expression is mechanistically linked to the promotion of cell migration. We also show that RIP-generated Jagged1 fragments exert disparate effects on PC3 cell behaviour and Notch signaling. In conclusion, the expression of both the full-length ligand and its RIP-generated fragments must be considered in tandem when attempting to regulate Jagged1 as a possible PCa therapy. - Highlights: • Bone marrow stroma induces Jagged1 expression in prostate cancer (PCa) PC3 cells. • This enhanced expression of full-length Jagged1 is required for PC3 cell migration. • Proteolytic fragments of Jagged1 exert disparate effects on PC3 cell behaviour. • Effects of fragments on cell behaviour do not correlate with Notch signaling. • Effects of Jagged1 and its fragments on PCa metastasis likely to be complex.},
doi = {10.1016/J.BBRC.2016.02.101},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 472,
place = {United States},
year = {2016},
month = {3}
}