title: TIS21/BTG2inhibits doxorubicin-induced stress fiber-vimentin networks via Nox4-ROS-ABI2-DRF-linked signal cascade.
abstract: Activities of TIS21/BTG2gene regulating cancer cell senescence were investigated in hepatoma cells by using low dose doxorubicin (Doxo, 100ng/mL). Treatment of Huh7 cells with Doxo increased linear actin nucleation e.g., transverse arcs and ventral stress fibers, as opposed to loss of filopodia. The linear actin nucleation was accompanied with thick vimentin networks at periphery of the cells, when examined by super-resolution STED microscope. However, expression of TIS21 inhibited ABI2-DRF pathway by inhibiting DRF expression and reducing ABI2 protein stability. The change lead to downregulation of stress fiber formations and thick vimentin networks at the periphery of Huh7 cells. In addition, TIS21 inhibited NADPH oxidase 4 (Nox4)-derived reactive oxygen species (ROS) generation that regulates actin nucleator, DRF family gene expression. Taken together, TIS21 attenuated Doxo-induced cancer cell senescence by inhibiting linear actin nucleation via Nox4-ROS-ABI2-DRF signal cascade, implying that expression of TIS21 overcomes resistance of senescent cells to cancer chemotherapy via inhibiting linear actin nucleation.
authors.affiliation: Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Republic of Korea; BK Plus program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Republic of Korea. Electronic address: iklim@ajou.ac.kr.
authors.forename: In Kyoung
authors.initials: IK
authors.lastname: Lim
authors.affiliation: Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Republic of Korea.
authors.forename: Jung-A
authors.initials: JA
authors.lastname: Choi
authors.affiliation: BK Plus program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Republic of Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kim
authors.affiliation: BK Plus program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Republic of Korea.
authors.forename: Bit Na
authors.initials: BN
authors.lastname: Kim
authors.affiliation: Department of Chemistry, Korea University, Seoul 02841, Republic of Korea.
authors.forename: Soohyun
authors.initials: S
authors.lastname: Jang
authors.affiliation: BK Plus program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Republic of Korea.
authors.forename: Min Sook
authors.initials: MS
authors.lastname: Ryu
authors.affiliation: Department of Chemistry, Korea University, Seoul 02841, Republic of Korea.
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Shim
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D005810:Multigene Family; D000074663:NADPH Oxidase 4 / Q000378:metabolism*; D010641:Phenotype; D055550:Protein Stability / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D022502:Stress Fibers / Q000187:drug effects / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism*
chemical_list: C096831:ABI2 protein, human; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D017874:Immediate-Early Proteins; D017382:Reactive Oxygen Species; D025521:Tumor Suppressor Proteins; D014746:Vimentin; C070114:BTG2 protein, human; D004317:Doxorubicin; D000074663:NADPH Oxidase 4
keywords: Abl-interactor 2 (ABI2); Actin stress fiber; Diaphanous-related formin (DRF); NADPH oxidase 4 (Nox4); Reactive oxygen species (ROS); Vimentin