PT  - JOURNAL ARTICLE
AU  - JAE-WOOK LEE
AU  - JIYOUNG LEE
AU  - EUN-YI MOON
TI  - HeLa Human Cervical Cancer Cell Migration Is Inhibited by Treatment with Dibutyryl-cAMP
DP  - 2014 Jul 01
TA  - Anticancer Research
PG  - 3447--3455
VI  - 34
IP  - 7
4099  - http://ar.iiarjournals.org/content/34/7/3447.short
4100  - http://ar.iiarjournals.org/content/34/7/3447.full
SO  - Anticancer Res2014 Jul 01; 34
AB  - Cyclic AMP (cAMP) activates both protein kinase A (PKA) and guanine-nucleotide exchange factor exchange protein directly activated by CAMP (EPAC)-mediated Ras-related Protein1 (RAP1) GTPase that regulates various cellular functions including cell migration. Herein, we investigated whether cAMP-mediated PKA and EPAC1/RAP1 pathways differentially control HeLa cervical cancer cell migration. Although HeLa cell migration was reduced by dibutyryl-cAMP, we observed an increase in cAMP/PKA, cAMP/EPAC1/RAP1-GTPase, and RAC1-GTPase. HeLa cell migration and RAC1-GTPase were increased by treatment with 8-(4-chloro-phenylthio)-2’-O-methyladenosine-3’,5’-cAMP analogue to activate EPAC-specific signaling pathways. When HeLa cells were treated with H-89, a PKA inhibitor, cell migration was enhanced but RAC1-GTPase was inhibited. In addition, cell migration induced by dibutyryl-cAMP was reversed but the activity of Rac1-GTPase was inhibited by H-89 treatment. Taken together, these data demonstrate that cAMP/PKA and cAMP/EPAC1/RAP1-GTPase might inversely control cervical cancer cell migration, although both signaling pathways may up-regulate RAC1-GTPase. It also suggests that cAMP-mediated cancer cell migration was independent of RAC1-GTPase activation.