title: The small molecule genkwanine M induces single mode, mesenchymal tumor cell motility.
abstract: Individual tumor cells utilize one of two modes of motility to invade the extracellular matrix, mesenchymal or amoeboid. We have determined that the diterpenoid genkwanine M (GENK) enhances the mesenchymal mode of cell motility that is intrinsic to HT-1080 osteosarcoma cells, stimulates a mesenchymal mode of motility in stationary MDA-MB-453 breast carcinoma cells, and induces a shift to a mesenchymal mode of cell motility in LS174T colorectal adenocarcinoma cells that normally utilize the alternate amoeboid mode of motility. The ability of GENK to stimulate or induce mesenchymal motility was preceded by a rapid cell spreading, elongation and polarization that did not require new gene expression. However, these initial morphologic changes were integrin dependent and they were associated with a reorganization of focal contacts and focal adhesions as well as an activation of the focal adhesion kinase. Therefore, GENK induces a mesenchymal mode of cell motility in a wide variety of tumor cell types that may be mediated, at least in part, by an activation of integrin-associated signaling.
authors: Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
authors: Carla
authors: C
authors: Zimmerman
authors: Pamela
authors: P
authors: Austin
authors: Anthony
authors: A
authors: Khong
authors: Sarah
authors: S
authors: McLeod
authors: Bjorn
authors: B
authors: Bean
authors: Roberto
authors: R
authors: Forestieri
authors: Raymond J
authors: RJ
authors: Andersen
authors: Eric
authors: E
authors: Jan
authors: Michel
authors: M
authors: Roberge
authors: Calvin D
authors: CD
authors: Roskelley
mesh_terms: D049108:Cell Enlargement / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D016764:Cell Polarity; D048430:Cell Shape / Q000187:drug effects*; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D022001:Focal Adhesions; D006801:Humans; D039001:Integrin alpha Chains / Q000737:chemistry; D039641:Integrin beta Chains / Q000737:chemistry; D009361:Neoplasm Invasiveness / Q000473:pathology; D012516:Osteosarcoma / Q000737:chemistry / Q000473:pathology; D014176:Protein Biosynthesis / Q000187:drug effects; D014158:Transcription, Genetic; D032365:Wikstroemia / Q000737:chemistry
chemical_list: D047309:Flavones; D039001:Integrin alpha Chains; D039641:Integrin beta Chains; C014568:genkwanin