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

In Kyoung Lim, Jung A. Choi, Eun Young Kim, Bit Na Kim, Soohyun Jang, Min Sook Ryu, Sang-Hee Shim

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Activities of TIS21 /BTG2 gene regulating cancer cell senescence were investigated in hepatoma cells by using low dose doxorubicin (Doxo, 100 ng/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.

Original languageEnglish
Pages (from-to)179-190
Number of pages12
JournalCellular Signalling
Volume30
DOIs
Publication statusPublished - 2017 Jan 1

Fingerprint

Stress Fibers
NADPH Oxidase
Vimentin
Doxorubicin
Actins
Reactive Oxygen Species
Cell Aging
Pseudopodia
Protein Stability
Neoplasm Genes
Hepatocellular Carcinoma
Neoplasms
Down-Regulation
Gene Expression
Drug Therapy

Keywords

  • Abl-interactor 2 (ABI2)
  • Actin stress fiber
  • Diaphanous-related formin (DRF)
  • NADPH oxidase 4 (Nox4)
  • Reactive oxygen species (ROS)
  • Vimentin

ASJC Scopus subject areas

  • Cell Biology

Cite this

TIS21 /BTG2 inhibits doxorubicin-induced stress fiber-vimentin networks via Nox4-ROS-ABI2-DRF-linked signal cascade . / Lim, In Kyoung; Choi, Jung A.; Kim, Eun Young; Kim, Bit Na; Jang, Soohyun; Ryu, Min Sook; Shim, Sang-Hee.

In: Cellular Signalling, Vol. 30, 01.01.2017, p. 179-190.

Research output: Contribution to journalArticle

Lim, In Kyoung ; Choi, Jung A. ; Kim, Eun Young ; Kim, Bit Na ; Jang, Soohyun ; Ryu, Min Sook ; Shim, Sang-Hee. / TIS21 /BTG2 inhibits doxorubicin-induced stress fiber-vimentin networks via Nox4-ROS-ABI2-DRF-linked signal cascade In: Cellular Signalling. 2017 ; Vol. 30. pp. 179-190.
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