10163

WASF2

WAS protein family, member 2;WASF2;WAS protein family, member 2

WASP family Verprolin-homologous protein 2|WASP family protein member 2|WASP family protein member 4|protein WAVE-2|putative Wiskott-Aldrich syndrome protein family member 4|suppressor of cyclic-AMP receptor (WASP-family)|verprolin homology domain-contain

1p36.11

protein-coding

Directed movement of normal cells occurs when actin-related protein 2 and 3 complex (Arp2/3 complex) triggers the actin polymerization that forms lamellipodia immediately after binding to WAVE2. In order to determine whether the same mechanism correlates with liver metastasis from colorectal cancer, paired mirror sections of 154 cancer specimens (29 cases with liver metastasis and 125 cases without liver metastasis in which T factor, gender, primary tumor site, and age at operation were matched) were examined immunohistochemically for the localization of Arp2 and WAVE2. expression of both Arp2 and WAVE2 was detected in the same cancer cells in 55 (35.7%) of the 154 cases, but not detected in the normal colonic epithelial cells. Univariate analysis showed that the colocalization was significantly predictive of liver metastasis (risk ratio [RR] 8.760. Likewise, histological grade (RR 2.46), lymphatic invasion (RR 9.95), and tumor budding (RR 4.00) were significant predictors. Among these, colocalization and lymphatic invasion were shown to be independent risk factors by multivariate analysis. Another 59 colorectal specimens were examined for mRNA expression of Arp2 by real time polymerase chain reaction. High mRNA levels of Arp2, that in situ hybridization revealed to be expressed by the cancer cells, were significantly associated with liver metastasis. However, its effect was absorbed by the influence of risk of the colocalization that is closely related to high expression of Arp2. These results indicate that the colocalization of Arp2 and WAVE2 is an independent risk factor for liver metastasis of colorectal carcinoma.

The small protein, HSPC300 (haematopoietic stem/progenitor cell protein 300), is associated with reorganization of actin filaments and cell movement, but its activity has not been reported in human cancer cells. Here, we investigated the association of HSPC300 expression with clinical features of lung squamous cell carcinoma. High levels of HSPC300 protein were detected in 84.1% of tumour samples, and in 30.8% of adjacent morphologically normal tissues. The number of primary tumours with elevated HSPC300 levels was significantly higher in primary tumours with lymph node metastases as opposed to those without, and also in tumours from patients with more advanced disease. HSPC300 modulates the morphology and motility of cells, as siRNA knockdown caused the reorganization of actin filaments, decreased the formation of pseudopodia, and inhibited the migration of a lung cancer cell line. We further showed that HSPC300 interacted with the WAVE2 protein, and HSPC300 silencing resulted in the degradation of WAVE2 in vitro. HSPC300 and WAVE2 were co-expressed in approximately 85.7% of primary tumours with lymph node metastases. We hypothesize that HSPC300 is associated with metastatic potential of lung squamous cell carcinoma through its interaction with WAVE2.