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Updated: May 20, 2026

RhoC GTPase Activation Assay
Published on: August 22, 2010
BART inhibits pancreatic cancer cell invasion by Rac1 inactivation through direct binding to active Rac1
Keisuke Taniuchi1, Kunihiko Yokotani, Toshiji Saibara
1Department of Pharmacology, School of Medicine, Kochi University, Nankoku, Kochi, Japan. ktaniuchi@kochi-u.ac.jp
Abstract:
We report that Binder of Arl Two (BART) plays a role in inhibiting cell invasion by regulating the activity of the Rho small guanosine triphosphatase protein Rac1 in pancreatic cancer cells. BART was originally identified as a binding partner of ADP-ribosylation factor-like 2, a small G protein implicated as a regulator of microtubule dynamics and folding. BART interacts with active forms of Rac1, and the BART-Rac1 complex localizes at the leading edges of migrating cancer cells. Suppression of BART increases active Rac1, thereby increasing cell invasion. Treatment of pancreatic cancer cells in which BART is stably knocked down with a Rac1 inhibitor decreases invasiveness. Thus, BART-dependent inhibition of cell invasion is likely associated with decreased active Rac1. Suppression of BART induces membrane ruffling and lamellipodial protrusion and increases peripheral actin structures in membrane ruffles at the edges of lamellipodia. The Rac1 inhibitor inhibits the lamellipodia formation that is stimulated by suppression of BART. Our results imply that BART regulates actin-cytoskeleton rearrangements at membrane ruffles through modulation of the activity of Rac1, which, in turn, inhibits pancreatic cancer cell invasion.
Insights
Binder of Arl Two (BART) inhibits pancreatic cancer cell invasion by regulating Rac1 activity. BART suppression increases Rac1 activity and cell invasion, while Rac1 inhibitors reduce invasiveness.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Binder of Arl Two (BART) is a protein interacting with ADP-ribosylation factor-like 2, involved in microtubule dynamics.
- The Rho GTPase protein Rac1 is implicated in cell migration and invasion processes.
Purpose of the Study:
- To investigate the role of BART in regulating pancreatic cancer cell invasion.
- To elucidate the mechanism by which BART affects cell invasion, focusing on its interaction with Rac1.
Main Methods:
- Investigated BART's interaction with active Rac1 in pancreatic cancer cells.
- Assessed the impact of BART suppression on Rac1 activity and cell invasion.
- Utilized Rac1 inhibitors to evaluate their effect on invasiveness in BART-knockdown cells.
- Observed actin-cytoskeleton rearrangements, including membrane ruffling and lamellipodia formation.
Main Results:
- BART interacts with active Rac1 at the leading edges of migrating cancer cells.
- Suppression of BART leads to increased active Rac1 and enhanced cell invasion.
- Rac1 inhibition reduces invasiveness in pancreatic cancer cells with suppressed BART.
- BART suppression induces membrane ruffling and lamellipodia formation, dependent on Rac1 activity.
Conclusions:
- BART inhibits pancreatic cancer cell invasion by modulating Rac1 activity.
- The BART-Rac1 complex regulates actin-cytoskeleton rearrangements crucial for invasion.
- Targeting the BART-Rac1 pathway may offer therapeutic strategies for pancreatic cancer.
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