Anti-ARPC2 (aa 288-300) polyclonal antibody

Metastasis is the leading cause of cancer mortality and cancer cell migration is an essential stage of metastasis. We identified benproperine (Benp, a clinically used antitussive drug) as an inhibitor of cancer cell migration and an anti-metastatic agent. Benp selectively inhibited cancer cell migration and invasion, which also suppressed metastasis of cancer cells in animal models. Actin-related protein 2/3 complex subunit 2 (ARPC2) was identified as a molecular target of Benp by affinity column chromatography with Benp-tagged Sepharose beads. Benp bound directly to ARPC2 in cells, which was validated by pull-down assay using Benp-biotin and label-free biochemical methods such as the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA). Benp inhibited Arp2/3 function, showing disruption of lamellipodial structure and inhibition of actin polymerization. Unlike Arp2/3 inhibitors, Benp selectively inhibited the migration of cancer cells but not normal cells. ARPC2-knockdown cancer cells showed defective cell migration and suppressed metastasis in an animal model. Therefore, ARPC2 is a potential target for anti-metastatic therapy, and Benp has the clinical potential to block metastasis. Furthermore, Benp is a useful agent for studying the functions of the Arp2/3 complex in cancer cell migration and metastasis.

Background: Actin-related protein 2/3 (ARP2/3) complex is an actin nucleator responsible for actin cytoskeleton branching which is essential for efficient cell migration. Materials and Methods: The expression of the seven ARP2/3 complex subunits was assessed in pancreatic cancer cell lines and in normal pancreatic samples by quantitative RT-PCR. siRNA-mediated silencing was used to study the contribution of each ARP2/3 complex member to pancreatic cancer cell migration. Results: ARPC3 and ARPC4 were the most highly expressed complex members, while ARPC1B and ARPC2 were expressed at low levels. Silencing of the ARP2/3 complex subunits typically resulted in reduced cell migration capacity. In particular, silencing of ARPC4 significantly reduced cell migration in all studied cell lines, with a major impact on Hs700T and HPAFII migration (50% and 68% decrease, p < 0.001). Conclusion: We offer comprehensive expression data on the ARP2/3 complex members for pancreatic cancer and normal pancreas. In addition, we show cell line-specific differences in ARP2/3 complex subunit dependency on cell migratory potential, and suggest ARPC4 to be one of the key members of the ARP2/3 complex in pancreatic cancer.