title: HeLa human cervical cancer cell migration is inhibited by treatment with dibutyryl-cAMP.
abstract: 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.
authors: Department of Bioscience and Biotechnology, Sejong University, Seoul, Repubic of Korea.
authors: Jae-Wook
authors: JW
authors: Lee
authors: Department of Bioscience and Biotechnology, Sejong University, Seoul, Repubic of Korea.
authors: Jiyoung
authors: J
authors: Lee
authors: Department of Bioscience and Biotechnology, Sejong University, Seoul, Repubic of Korea.
authors: Eun-Yi
authors: EY
authors: Moon
mesh_terms: D003994:Bucladesine / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C107953:RAC1 protein, human; C116122:RAPGEF3 protein, human; D000089804:Shelterin Complex; C440809:TERF2IP protein, human; D034501:Telomere-Binding Proteins; D003994:Bucladesine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D020558:GTP Phosphohydrolases; D020830:rac1 GTP-Binding Protein
keywords: EPAC1/RAP1; PKA; RAC1; cAMP; cell migration