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

Delury, Craig Phillip and Hart, Claire and Brown, Mick and Clarke, Noel and Parkin, Edward Thomas (2016) Stroma-induced Jagged1 expression drives PC3 prostate cancer cell migration:disparate effects of RIP-generated proteolytic fragments on cell behaviour and Notch signaling. Biochemical and Biophysical Research Communications, 472 (1). pp. 255-261. ISSN 0006-291X

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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.

Item Type:
Journal Article
Journal or Publication Title:
Biochemical and Biophysical Research Communications
Additional Information:
This is the author’s version of a work that was accepted for publication in Biochemical and Biophysical Research Communications. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biochemical and Biophysical Research Communications, 472, 1, 2016 DOI: 10.1016/j.bbrc.2016.02.101
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1300/1304
Subjects:
ID Code:
78635
Deposited By:
Deposited On:
19 Apr 2016 12:38
Refereed?:
Yes
Published?:
Published
Last Modified:
09 Aug 2020 04:06