Rights statement: 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
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Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Stroma-induced Jagged1 expression drives PC3 prostate cancer cell migration
T2 - disparate effects of RIP-generated proteolytic fragments on cell behaviour and Notch signaling
AU - Delury, Craig Phillip
AU - Hart, Claire
AU - Brown, Mick
AU - Clarke, Noel
AU - Parkin, Edward Thomas
N1 - 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
PY - 2016/3/25
Y1 - 2016/3/25
N2 - 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.
AB - 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.
KW - Invasion
KW - Jagged1
KW - Metastasis
KW - Migration
KW - Notch signaling
KW - Prostate cancer
U2 - 10.1016/j.bbrc.2016.02.101
DO - 10.1016/j.bbrc.2016.02.101
M3 - Journal article
VL - 472
SP - 255
EP - 261
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -