DRAM1 regulates the migration and invasion of hepatoblastoma cells via autophagy-EMT pathway

Chao Chen1, Qing-Yu Liang2, Hui-Kang Chen1

  • 1Department of General Surgery, Changshu Second People's Hospital, The Fifth Hospital Affiliated to Yangzhou University, Changshu, Jiangsu 215500, P.R. China.

Oncology Letters
|July 18, 2018
PubMed

Insights

DNA-damage regulated autophagy modulator 1 (DRAM1) promotes cancer cell invasion. Inhibiting DRAM1 in hepatoblastoma cells reduced migration and invasion via the autophagy-epithelial-mesenchymal-transition (EMT) pathway.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • DNA-damage regulated autophagy modulator 1 (DRAM1) is a TP53 target involved in autophagy.
  • DRAM1 has been implicated in glioblastoma stem cell migration and invasion.
  • The precise role and mechanisms of DRAM1 in cancer cell invasion remain unclear.

Purpose of the Study:

  • To investigate the role of DRAM1 in hepatoblastoma cell migration and invasion.
  • To elucidate the underlying molecular mechanisms involving autophagy and epithelial-mesenchymal-transition (EMT).

Main Methods:

  • Knockdown of DRAM1 using siRNA and shRNA in hepatoblastoma cells (HepG2).
  • In vitro and in vivo assays to assess cell migration and invasion.
  • Western blotting and immunofluorescence to analyze autophagy proteins and EMT markers.
  • Treatment with rapamycin to assess pathway reversibility.

Main Results:

  • DRAM1 knockdown significantly inhibited hepatoma cell autophagy, migration, and invasion.
  • DRAM1 inhibition increased E-Cadherin expression and decreased vimentin expression, indicating suppressed EMT.
  • Rapamycin treatment partially reversed the effects of DRAM1 knockdown on autophagy and EMT markers.

Conclusions:

  • DRAM1 plays a crucial role in regulating hepatoma cell migration and invasion.
  • DRAM1 mediates these effects through the autophagy-EMT pathway.
  • Targeting DRAM1 may represent a therapeutic strategy for inhibiting cancer cell invasion.

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