ArticlePloS one2013
Investigation of tumor suppressing function of CACNA2D3 in esophageal squamous cell carcinoma.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 32 citations in OpenAlex.
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDeletion of 3p is one of the most frequent genetic alterations in esophageal squamous cell carcinoma (ESCC), suggesting the existence of one or more tumor suppressor genes (TSGs) within these regions. In this study, one TSG, CACNA2D3 at 3p21.1, was characterized.
methodsExpression of CACNA2D3 in ESCCs was tested by quantitative real-time PCR and tissue microarray. The mechanism of CACNA2D3 downregulation was investigated by methylation-specific polymerase chain reaction (MS-PCR). The tumor suppressive function of CACNA2D3 was characterized by both in vitro and in vivo tumorigenic assays, cell migration and invasion assays.
resultsCACNA2D3 was frequently downregulated in ESCCs (24/48, 50%), which was significantly associated with promoter methylation and allele loss (P<0.05). Tissue microarray result showed that downregulation of CACNA2D3 was detected in (127/224, 56.7%) ESCCs, which was significantly associated with lymph node metastasis (P = 0.01), TNM staging (P = 0.003) and poor outcome of ESCC patients (P<0.05). Functional studies demonstrated that CACNA2D3 could inhibit tumorigenicity, cell motility and induce apoptosis. Mechanism study found that CACNA2D3 could arrest cell cycle at G1/S checkpoint by increasing expressions of p21 and p53 and decreasing expression of CDK2. In addition, CACNA2D3 could upregulate intracellular free cytosolic Ca(2+) and subsequently induce apoptosis.
conclusionCACNA2D3 is a novel TSG responsible to the 3p21 deletion event and plays a critical suppressing role in the development and progression of ESCC.
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