10487

CAP1

CAP, adenylate cyclase-associated protein 1 (yeast);CAP1;CAP, adenylate cyclase-associated protein 1 (yeast)

CAP 1|adenylyl cyclase-associated protein 1

1p34.2

protein-coding

OBJECTIVE: Overexpression of cyclase-associated proteins has been associated with poor prognosis in several human cancers. Cyclase-associated protein 1 is a member of the cyclase-associated proteins which contributes to tumor progression. The aim of the present study was to examine the expression of cyclase-associated protein 1 and to elucidate its clinicopathologic signi fi cance in a larger series of esophageal squamous cell carcinoma. METHODS: Immunohistochemical and western blot analyses were performed in esophageal squamous cell carcinoma tissues. Survival analyses were performed by using the Kaplan-Meier method. The role of cyclase-associated protein 1 in migration was studied in esophageal squamous cell carcinoma cell lines of TE1 through knocking down cyclase-associated protein 1 with siRNA and overexpression of cyclase-associated protein 1. The regulation of cyclase-associated protein 1 on migration was determined by transwell and wound-healing assays. RESULTS: Immunohistochemical analysis showed that cyclase-associated protein 1 expression was negatively associated with E-cadherin and signi fi cantly associated with lymph node metastases. Survival analysis revealed that cyclase-associated protein 1 overexpression was signi fi cantly associated with overall survival (P = 0.011). Knock down of cyclase-associated protein 1 in TE1 cells resulted in decreased vimentin and F-actin levels and the capability for migration. In addition, overexpression of cyclase-associated protein 1 promoted the migration of TE1 cells. CONCLUSIONS: These fi ndings suggest that cyclase-associated protein 1 is involved in the metastasis of esophageal squamous cell carcinoma, and that elevated levels of cyclase-associated protein 1 expression may indicate a poor prognosis for patients with esophageal squamous cell carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers that exhibits high incidences of intrahepatic metastasis and tumor recurrence. Adenylate cyclase-associated protein 1 (CAP1), a protein involved in the regulation of actin filaments, was recently reported to play a role in cell motility and the pathology of pancreatic cancer. In this study, we examined a potential role of CAP1 in HCC progression, and found that CAP1 was overexpressed in HCC specimens compared with adjacent noncancerous liver tissues by Western blot analysis and real-time PCR assay. Further, immunohistochemical analysis in 107 HCC specimens revealed that overexpression of CAP1 was closely correlated only with tumor metastasis, but not with other clinicopathologic parameters. Univariate and multivariate survival analyses showed that CAP1 could be an independent prognostic factor for patients' survival. In addition, immunofluorescent assay demonstrated that CAP1 was colocalized with actin in the leading edge of lamellipodium in HCC cells. Importantly, knocking-down the expression of CAP1 using small interfering RNA (siRNA) targeting CAP1 led to impaired migration of HCC cells. Collectively, our results indicated that upregulated expression of CAP1 might contribute heavily to the metastasis of HCC.

Lung cancer ranks first in both prevalence and mortality rates among all types of cancer. metastasis is the main cause of treatment failure. Biomarkers are critical to early diagnosis and prediction and monitoring of progressive lesions. Several biomarkers have been identified for lung cancer but none have been routinely used clinically. The present study assessed the diagnostic and prognostic value of cyclase-associated protein 1 (CAP1) for lung cancer. CAP1 mRNA abundance and protein content were determined by real-time PCR and western blot analysis and/or immunostaining in biopsy specimens (24 neoplastic and 6 non-neoplastic) freshly collected at surgical lung resection, in 82 pathologically banked lung cancer specimens and in cultured non-invasive (95-C) and invasive (95-D) lung cancer cells. Multivariate regression analysis was performed to correlate immunoreactive CAP1 signal with cancer type and stage. In vitro cell migration was performed to determine the effect of RNA interference-mediated CAP1 gene silencing on invasiveness of 95-D cells. These analyses collectively demonstrated that: i) both CAP1 mRNA abundance and protein content were significantly higher in neoplastic compared to non-neoplastic specimens and in metastatic compared to non-metastatic specimens but not different between adenocarcinoma and squamous cell carcinoma; ii) immunoreactive CAP1 signal was significantly stronger in metastatic specimens and 95-D cells compared to non-metastatic specimens and 95-C cells; and iii) RNA interference-mediated CAP1 gene silencing adequately attenuated the invasive capacity of 95-D cells in vitro. These findings suggest that overexpression of CAP1 in lung cancer cells, particularly at the metastatic stage, may have significant clinical implications as a diagnostic/prognostic factor for lung cancer.