Overexpression of exchange protein directly activated by cAMP-1 (EPAC1) attenuates bladder cancer cell migration |
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| Authors: | Hirona Ichikawa Momoe Itsumi Shunichi Kajioka Tomoko Maki Ken Lee Makoto Tomita Shoji Yamaoka |
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| Affiliation: | 1. Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan;2. Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;3. Department of Applied Urology and Molecular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;4. Clinical Research Center, Medical Hospital of Tokyo Medical and Dental University, Tokyo, Japan |
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| Abstract: | 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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| Keywords: | Bladder cancer EPAC Cell migration Akt protein kinase B cAMP cyclic adenosine monophosphate EPAC exchange protein directly activated by cyclic adenosine monophosphate FBS fetal bovine serum GAPDH glyceraldehyde 3-phosphate dehydrogenase PKA protein kinase A Rap Ras-related protein ZO-1 zonula occludens-1 |
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