TY - JOUR
T1 - Overexpression of exchange protein directly activated by cAMP-1 (EPAC1) attenuates bladder cancer cell migration
AU - Ichikawa, Hirona
AU - Itsumi, Momoe
AU - Kajioka, Shunichi
AU - Maki, Tomoko
AU - Lee, Ken
AU - Tomita, Makoto
AU - Yamaoka, Shoji
N1 - Funding Information:
This work was supported by KAKENHI grants number for 15K20095 and 26462445 from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) . We would like to thank Dr. Hiroaki Takeuchi and Dr. Takashi Nagaishi (Tokyo Medical and Dental University, Japan) for skilled assistance, and Ms. Mika Nabeta, Ms. Noriko Hakoda and Ms. Eriko Gunshima (Kyusyu University, Japan) for their technical assistance and support in the experiments utilizing bladder tissues from patients. We also thank www.oxmedcomms.com for writing assistance.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbrc.2017.10.142
DO - 10.1016/j.bbrc.2017.10.142
M3 - Article
C2 - 29111327
AN - SCOPUS:85032951612
VL - 495
SP - 64
EP - 70
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -