RESUMO
BACKGROUND: TSP50 (testes-specific protease 50) has been reported to be a candidate oncogene and is overexpressed in various cancers. Our previous study demonstrated that TSP50 protein is elevated in gastric cancer, and its high expression is associated with unfavorable prognosis and lymph node metastasis. However, the role of TSP50 in gastric cancer remains elusive. METHODS: qRT-PCR, western blot were used to determine TSP50 expression in gastric cancer cell lines. Role of TSP50 in proliferation and invasion was examined by BrdU incorporation assay, cell count, wound healing and transwell assay. Immunohistochemistry and western blot were performed to identify the potential mechanisms involved. RESULTS: TSP50 was highly expressed in most of the gastric cancer cell lines at both mRNA and protein levels. Up-regulation of TSP50 in gastric cancer cells enhanced proliferation and invasiveness, whereas down-regulation of TSP50 by its specific shRNA decreased it. A negative correlation between TSP50 and E-Cadherin was found in gastric cancer tissues, and combination of them improves the prediction for prognosis and lymph node metastasis. Mechanistic studies revealed that overexpression of TSP50 increased the expression of epithelial-to-mesenchymal transition (EMT) markers including Vimentin, and Twist, and decreased the epithelial marker E-Cadherin. NF-κB signaling pathway is involved in the regulatory effects of TSP50 on EMT, migration and invasion in gastric cancer cells. CONCLUSION: TSP50 promotes the proliferation, migration and invasion of gastric cancer cells involving NF-κB dependent EMT activation. Targeting TSP50 may provide a novel therapeutic strategy for the management of gastric cancer.
Assuntos
Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Serina Endopeptidases/genética , Neoplasias Gástricas/genética , Caderinas/genética , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , NF-kappa B/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neoplasias Gástricas/patologia , Testículo/metabolismoAssuntos
Proteínas Serina-Treonina Quinases/fisiologia , Transdução de Sinais , Dente/crescimento & desenvolvimento , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Animais , Regulação da Expressão Gênica no Desenvolvimento , Via de Sinalização Hippo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Camundongos , Fosfoproteínas/fisiologia , Transativadores , Fatores de Transcrição , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Proteínas de Sinalização YAPRESUMO
We report a case of esophageal extranasal NK/T cell lymphoma with biphasic morphologic features revealed by a deep large piecemeal biopsy. A 40-year-old man present with pharyngalgia, dysphagia, recurrent fever, and 5-kg weight loss for 8 months. Endoscopy demonstrated progressing longitudinal ulcers and mucosal bridges along the esophagus. The first and second biopsies obtained superficial mucosa with scattered bland-looking small lymphocytes. A subsequent large piecemeal snare abscission for biopsy showed atypical lymphoid cells infiltrating into the deep lamina propria and muscularis mucosae, whereas the superficial lamina propria was highly edematous with scant small lymphocytes. Immunohistochemical studies confirmed that both underlying atypical cells and superficial small lymphocytes were neoplastic, sharing an identical immunophenotype: positive for CD2, CD3, CD43, CD8, CD56, TIA-1 and granzyme B. Epstein-Barr virus-encoded small RNAs were found in both cells. The histologic findings were diagnostic of primary esophageal extranasal NK/T cell lymphoma. However, the patient developed bone marrow depression during chemotherapy and died of massive cerebral hemorrhage after the first cycle of chemotherapy. Primary esophageal extranodal NK/T cell lymphoma nasal type is extremely rare. We show the biphasic morphology of this disease, which highlights the importance of deep biopsy for accurate diagnosis.