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BART inhibits pancreatic cancer cell invasion by inhibiting ARL2-mediated RhoA inactivation

Keisuke Taniuchi1, Shinji Iwasaki, Toshiji Saibara

  • 1Department of Gastro-enterology and Hepatology, Kochi University Medical School, Nankoku, Kochi 783-8505, Japan. jm-ktaniuchi@kochi-u.ac.jp

International Journal of Oncology
|August 12, 2011
PubMed

Insights

BART protein inhibits pancreatic cancer cell invasion by regulating RhoA activity. BART prevents ARL2 from inactivating RhoA, thus increasing active RhoA and decreasing cell invasion.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • BART protein identified as a binding partner of ARL2, a small G-protein involved in microtubule dynamics.
  • Rho GTPase protein RhoA plays a critical role in cell migration and invasion.

Purpose of the Study:

  • To investigate the role of BART in pancreatic cancer cell invasion.
  • To elucidate the mechanism by which BART regulates RhoA activity.

Main Methods:

  • RNA interference (RNAi) for BART knockdown.
  • Analysis of protein-protein interactions (BART, ARL2, RhoA).
  • Assessment of cell invasion assays.
  • Investigation of actin-cytoskeleton rearrangements.

Main Results:

  • BART interacts with GTP-bound ARL2 and prevents its inactivation of RhoA at the leading edge of migrating cancer cells.
  • BART binding to ARL2 increases the amount of active RhoA, thereby inhibiting cell invasion.
  • Knockdown of BART or treatment with a Rho inhibitor (C3 exoenzyme) significantly increases pancreatic cancer cell invasion.

Conclusions:

  • BART acts as an inhibitor of ARL2 at the leading edge of migrating cells, leading to increased active RhoA.
  • This BART-mediated regulation of RhoA activity is crucial for inhibiting pancreatic cancer cell invasion and actin-cytoskeleton rearrangements.

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