Involvement of Arp2/3 complex in the process of colorectal carcinogenesis

Abstract

Increased motility is one of the characteristics of cancer cells, and actin polymerization and disassembly are essential for cellular motility. Since actin-related protein (Arp) 2/3 complex acts as a nucleus for actin polymerization, in this study, we immunohistochemically investigated the expression of Arp2 and Arp3 in 175 colorectal tumors in various stages of neoplastic progression. Arp2 and Arp3 showed identical expression patterns, and both were expressed in the stromal cells around neoplastic tubules or glands and in the tumor cells themselves. The frequency of expression of Arp2 and Arp3 (Arp2&3) by the stromal cells increased with the atypia of the colorectal neoplasms, from 5.5% (3/55) in adenoma with mild or moderate atypia, to 11.8% (2/17) in adenoma with severe atypia, 53.3% (16/30) in intramucosal carcinoma, and 91.8% (67/73) in invasive carcinoma (Po0.0001). The frequency of expression of Arp2&3 in the tumor cells was similar and was 1.8% (1/55) in adenoma with mild or moderate atypia, 23.5% (4/17) in adenoma with severe atypia, 23.5% (7/30) in intramucosal carcinoma, and 32.9% (24/73) in invasive carcinoma. Expression of Arp2&3 by the stromal cells was significantly correlated with nuclear accumulation of p53 in the tumor cells and stromal expression of CD10. These results suggest that formation of Arp2/3 complex by both neoplastic and stromal cells contributes to the increased motility of both cell types and thus provides suitable conditions for invasion.

Molecular signatures of thyroid follicular neoplasia

“…In agreement with the clinical experience, we noted that cell-cycle mRNAs followed a gradient ranging from a few fold to more than 50-fold up-regulation, which may limit the isolated use of this parameter for diagnostic purposes. A number of the up-regulated transcripts including anillin , ARP 2/3 complex (Otsubo et al 2004), abnormal spindle homolog (Ayllon & O'connor 2007, Lin et al 2008, centromere protein F (Campone et al 2008), KIF4A (Taniwaki et al 2007), maternal embryonic leucine zipper kinase (Gray et al 2005), NIMA-related kinase 2 (Hayward & Fry 2006), PDZ-binding kinase, protein regulator of cytokinesis 1 (Boukarabila et al 2009), regulator of chromosome condensation 2 (Stacey et al 2008), encoded proteins that are directly involved in mitosis and several of them are over-expressed in other cancers. In particular, transcripts encoding ribonucleotide reductase small subunit, RRM2, and topoisomerase 2a, TOP2A respectively, are intimately connected to cancer.…”

The interplay between the proteolytic, invasive, and adhesive domains of invadopodia and their roles in cancer invasion

“…90,91 Stabilization of the actin polymerization capacity of the Arp 2/3 complex is attributed to the binding of Arp 2/3 to both N-WASP and cortactin, the latter also binds to actin, and stabilizes the filament. 76,92,93 (3) Cortactin is a cytoskeletal, multi-domain protein that is important for the induction of actin polymerization.…”

Ets1 is an effector of protein kinase Cα in cancer cells

“…Arp2/3 is involved in the regulation of actin filament in branching and essential for actin-based motility (Carlier et al, 2003). In invasive colorectal cancer expression of Arp2 and Arp3 is increased (Otsubo et al, 2004). This suggests that the Arp2/3 complex is involved in tumor progression.…”

“…Six genes (NQO1, MMP1, MMP9, ARPC2, ARHG-DIB and PEG10) of the 32 genes have been reported to be associated with tumor progression (Behrens et al, 2001;Sunaga et al, 2002;Lin et al, 2003;Okabe et al, 2003;Otsubo et al, 2004). Except PEG10, all of these genes were found to be downregulated along with Ets1 and PKCa.…”