Overexpression of exchange protein directly activated by cAMP-1 (EPAC1) attenuates bladder cancer cell migration

Exchange protein directly activated by cAMP (EPAC) is a mediator of a cAMP signaling pathway that is independent of protein kinase A. EPAC has two isoforms (EPAC1 and EPAC2) and is a cAMP-dependent guanine nucleotide exchange factor for the small GTPases, Rap1 and Rap2. Recent studies suggest that E...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2018-01, Vol.495 (1), p.64-70
Main Authors: Ichikawa, Hirona, Itsumi, Momoe, Kajioka, Shunichi, Maki, Tomoko, Lee, Ken, Tomita, Makoto, Yamaoka, Shoji
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
APOPTOSIS
BLADDER
Bladder cancer
Cell migration
CELL PROLIFERATION
EPAC
GUANINE
MESSENGER-RNA
NEOPLASMS
PHOSPHOTRANSFERASES
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Summary:Exchange protein directly activated by cAMP (EPAC) is a mediator of a cAMP signaling pathway that is independent of protein kinase A. EPAC has two isoforms (EPAC1 and EPAC2) and is a cAMP-dependent guanine nucleotide exchange factor for the small GTPases, Rap1 and Rap2. Recent studies suggest that EPAC1 has both positive and negative influences on cancer and is involved in cell proliferation, apoptosis, migration and metastasis. We report that EPAC1 and EPAC2 expression levels were significantly lower in bladder cancer tissue than in normal bladder tissue. In addition, bladder cancer cell lines showed reduced EPAC1 mRNA expression. Furthermore, EPAC1 overexpression in bladder cancer cell lines induced morphologic changes and markedly suppressed cell migration without affecting cell viability. The overexpressed EPAC1 preferentially localized at cell-cell interfaces. In conclusion, reduced EPAC1 expression in bladder tumors and poor migration of EPAC1-overexpressing cells implicate EPAC1 as an inhibitor of bladder cancer cell migration. •Bladder tumors showed poor expression of EPAC1.•Overexpression of EPAC1 suppressed migration of bladder cancer cells.•Rap1 was persistently activated in EPAC1-overexpressing cells.•Overexpression of EPAC1 preferentially localized at cell-cell interfaces.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2017.10.142