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TIS21(/BTG2) inhibits doxorubicin-induced stress fiber-vimentin networks via Nox4-ROS-ABI2-DRF-linked signal cascade

Authors
Lim, IK  | Choi, JA | Kim, EY | Kim, BN | Jang, S | Ryu, MS  | Shim, SH
Citation
Cellular signalling, 30. : 179-190, 2017
Journal Title
Cellular signalling
ISSN
0898-65681873-3913
Abstract
Activities of TIS21(/BTG2) gene 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.
MeSH

DOI
10.1016/j.cellsig.2016.12.001
PMID
27932314
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
Ajou Authors
유, 민숙  |  임, 인경
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