title: LIM domain only 2 induces glioma invasion via cytosolic p27(KIP1).
abstract: High-grade gliomas are considered the most malignant of brain tumors and have a poor prognosis. In a previous study, we showed that LIM domain only 2 (LMO2) regulates glioma stem cell properties and tumor angiogenesis and gave rise to highly invasive glioma xenografts. Glioma invasion in the surrounding parenchymal tissues is a major hurdle with respect to eliminating glioma by surgery. Invasive glioma cells are considered one of the main culprits for the recurrence of tumors after therapies. In the current study, we focused on determining the molecular mechanism(s) by which LMO2 regulates glioma cell migration and invasion. Forced expression of LMO2 in human U87MG glioma cells led to glioma invasion, as determined by in vivo xenograft assays and enhanced in vitro migration and invasion. LMO2 was associated with increased levels of cytosolic p27(Kip1) protein. LMO2 possibly induced the stabilization and augmented interactions between p27(Kip1) and RhoA. We knocked down the expression of p27(Kip1), which led to a decrease in LMO2-driven glioma cell migration and invasion. Taken together, our findings indicate that LMO2 promotes glioma cell migration and invasion by increasing the levels of cytosolic p27(Kip1).
authors.affiliation: Department of Biotechnology, School of Life Science and Biotechnology, Korea University, Seoul, 136-713, Republic of Korea.
authors.forename: Cheol Gyu
authors.initials: CG
authors.lastname: Park
authors.affiliation: Department of Biotechnology, School of Life Science and Biotechnology, Korea University, Seoul, 136-713, Republic of Korea.
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Sohn
authors.affiliation: Department of Biotechnology, School of Life Science and Biotechnology, Korea University, Seoul, 136-713, Republic of Korea.|Institute of Animal Molecular Biotechnology, Korea University, Seoul, 136-713, Republic of Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, School of Life Science and Biotechnology, Korea University, Seoul, 136-713, Republic of Korea.|Department of Neurological Surgery, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
authors.forename: Sung-Hak
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Medicine, Hallym University, Chuncheon, 200-702, Republic of Korea. biokim@hallym.ac.kr.
authors.forename: Sung-Chan
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, School of Life Science and Biotechnology, Korea University, Seoul, 136-713, Republic of Korea. hg-kim@korea.ac.kr.|Institute of Animal Molecular Biotechnology, Korea University, Seoul, 136-713, Republic of Korea. hg-kim@korea.ac.kr.
authors.forename: Hyunggee
authors.initials: H
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism* / Q000473:pathology; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D057809:HEK293 Cells; D006801:Humans; D060588:LIM Domain Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C436291:CDKN1B protein, human; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D011518:Proto-Oncogene Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D020742:rhoA GTP-Binding Protein
keywords: Cell invasion; Cell migration; Glioma; LMO2; RhoA; p27Kip1