RESUMEN
BACKGROUND: Lamina-associated polypeptides 2 (LAP2) is a nuclear protein that connects the nuclear lamina with chromatin. Although its critical roles in genetic disorders and hematopoietic malignancies have been described, its expression and roles in digestive tract cancers have been poorly characterized. METHODS: To examine the expression of LAP2 in patient tissues, we performed immunohistochemistry and real-time PCR. To examine motility of cancer cells, we employed Boyden chamber, wound healing and Matrigel invasion assays. To reveal its roles in metastasis in vivo, we used a liver metastasis xenograft model. To investigate the underlying mechanism, a cDNA microarray was conducted. RESULTS: Immunohistochemistry in patient tissues showed widespread expression of LAP2 in diverse digestive tract cancers including stomach, pancreas, liver, and bile duct cancers. Real-time PCR confirmed that LAP2ß is over-expressed in gastric cancer tissues. Knockdown of LAP2ß did not affect proliferation of most digestive tract cancer cells except pancreatic cancer cells. However, knockdown of LAP2ß decreased motility of all tested cancer cells. Moreover, overexpression of LAP2ß increased motility of gastric and pancreatic cancer cells. In the liver metastasis xenograft model, LAP2ß increased metastatic efficacy of gastric cancer cells and mortality in tested mice. cDNA microarrays showed the possibility that myristoylated alanine-rich C kinase substrate (MARCKS) and interleukin6 (IL6) may mediate LAP2ß-regulated motility of cancer cells. CONCLUSIONS: From the above results, we conclude that LAP2 is widely overexpressed in diverse digestive tract cancers and LAP2ß regulates motility of cancer cells and suggest that LAP2ß may have utility for diagnostics and therapeutics in digestive tract cancers.
Asunto(s)
Proteínas de Unión al ADN/metabolismo , Neoplasias Gastrointestinales/metabolismo , Proteínas de la Membrana/metabolismo , Animales , Western Blotting , Línea Celular Tumoral , Movimiento Celular/genética , Movimiento Celular/fisiología , Proliferación Celular , Proteínas de Unión al ADN/genética , Neoplasias Gastrointestinales/genética , Humanos , Inmunohistoquímica , Proteínas de la Membrana/genética , Ratones , Ratones Desnudos , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Glioblastoma is the most common type of astrocytoma in the brain. Due to its high invasiveness and chemoresistance, patients with advanced stage of glioblastoma have a poor prognosis. SNAI1, an important regulator of epithelial-mesenchymal transition, has been associated with metastasis in various carcinoma cells. However, its roles in glioblastoma cells have been poorly characterized. To examine roles of SNAI1 in glioblastoma cells, we knockdowned SNAI1 expression using siRNA. SNAI1 siRNA increased the expression level of E-cadherin and decreased that of vimentin. In the water-soluble tetrazolium salt (WST-1) assay, SNAI1 siRNA inhibited the proliferation of U87-MG and GBM05 glioblastoma cells. Moreover, in the Boyden chamber assay and Matrigel invasion assay, SNAI1 siRNA inhibited serum-induced migration and invasion of glioblastoma cells. These results suggested that SNAI1 is involved in the proliferation and migration of glioblastoma cells.
