title: Glucocorticoid receptor-mediated expression of caldesmon regulates cell migration via the reorganization of the actin cytoskeleton.
abstract: Glucocorticoids (GCs) play important roles in numerous cellular processes, including growth, development, homeostasis, inhibition of inflammation, and immunosuppression. Here we found that GC-treated human lung carcinoma A549 cells exhibited the enhanced formation of the thick stress fibers and focal adhesions, resulting in suppression of cell migration. In a screen for GC-responsive genes encoding actin-interacting proteins, we identified caldesmon (CaD), which is specifically up-regulated in response to GCs. CaD is a regulatory protein involved in actomyosin-based contraction and the stability of actin filaments. We further demonstrated that the up-regulation of CaD expression was controlled by glucocorticoid receptor (GR). An activated form of GR directly bound to the two glucocorticoid-response element-like sequences in the human CALD1 promoter and transactivated the CALD1 gene, thereby up-regulating the CaD protein. Forced expression of CaD, without GC treatment, also enhanced the formation of thick stress fibers and focal adhesions and suppressed cell migration. Conversely, depletion of CaD abrogated the GC-induced phenotypes. The results of this study suggest that the GR-dependent up-regulation of CaD plays a pivotal role in regulating cell migration via the reorganization of the actin cytoskeleton.
authors.affiliation: Research Center for Child Mental Development, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Taira
authors.initials: T
authors.lastname: Mayanagi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Morita
authors.forename: Ken'ichiro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Fukumoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Sobue
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D000199:Actins; D002148:Calmodulin-Binding Proteins; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid
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