RESUMEN

BACKGROUND/AIM: Overexpression of erythropoietin-producing hepatocellular A1 (EPHA1), a member of the EPH super family, is frequently observed in various cancer types. The dysregulated interaction of EPHA1 with its ligand Ephrin A1 has been linked to the progression of ovarian cancer (OC). However, the contribution of EPHA1 in the regulation of the aggressive properties of OC cells remains unknown. MATERIALS AND METHODS: In this study we investigated the differential expression of EPHA1 in human OC cells. The EPHA1 gene was knocked-down using the CRISPR/Cas9 technique to evaluate its effect on the progressive properties of OC cells. RESULTS: After EPHA1 was knocked-down using a CRISPR/CAS9 genomic editing system in OC cells (SKOV3 and COV504), we observed cell-cycle arrest at the G0/G1 phases in both OC cell lines. Knockdown of EPHA1 in the two OC cells inhibited their aggressive traits, including proliferation, invasion and migration, as well as improving their attachment to extracellular matrix. EPHA1 may play a role in OC through its regulation of multiple signaling pathways, such as matrix metalloproteinase-2 (MMP2), extracellular signal-regulated kinase 2 (ERK2) and proto-oncogene c-MYC. CONCLUSION: EPHA1 may promote the aggression of some OC cells and, thus, be considered a potential therapeutic target for the treatment of malignant OC.

Asunto(s)

Técnicas de Silenciamiento del Gen/métodos , Neoplasias Ováricas/metabolismo , Receptor EphA1/genética , Receptor EphA1/metabolismo , Sistemas CRISPR-Cas , Puntos de Control del Ciclo Celular , Movimiento Celular , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Invasividad Neoplásica , Neoplasias Ováricas/genética , Proto-Oncogenes Mas , Transducción de Señal

RESUMEN

BACKGROUND: Erythropoietin-producing hepatocellular A1 (EPHA1) is the first member of the EPH superfamily. Its abnormal expression has been reported in various cancer types. However, the contribution of EPHA1 to the regulation of colorectal cancer cell behaviour remains unknown. MATERIALS AND METHODS: In this study, we investigated the expression profile of EPHA1 in human colorectal cancer and its effect on the adhesion and motility of colorectal cancer cells. We used human colorectal cancer specimens and the colorectal adenocarcinoma cell line HRT18 for this purpose. RESULTS: Our cohort screening data showed that in patients with colorectal cancer, low expression of EPHA1 gene is correlated with a remarkably reduced survival. After EPHA1 is knocked-down in colorectal cancer cells using a clustered regularly interspaced short palindromic repeats-associated nuclease 9 (CRISPR-CAS9) genomic editing system, we observed an increase in the spreading and adhesion of HRT18 cells. Moreover, protein array data indicated that the extracellular-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) signaling pathways were activated as a consequence. Inhibition of ERK and JNK proteins with specific inhibitors led to suppression of migration of the colorectal cancer cells. CONCLUSION: EPHA1 suppresses spreading and adhesion of HRT18 colorectal cancer cells through deactivation of ERK and JNK signaling pathways.

Asunto(s)

Adenocarcinoma/metabolismo , Sistemas CRISPR-Cas , Adhesión Celular , Movimiento Celular , Neoplasias Colorrectales/metabolismo , Técnicas de Silenciamiento del Gen , Receptor EphA1/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Forma de la Célula , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Activación Enzimática , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Estimación de Kaplan-Meier , Invasividad Neoplásica , Inhibidores de Proteínas Quinasas/farmacología , Receptor EphA1/genética , Transducción de Señal , Factores de Tiempo , Transfección

RESUMEN

Primitive neuroectodermal tumor (PNET) is most commonly encountered in the soft tissue or bone in children and young adults, and its involvement in the intestines is exceedingly rare. To the best of our knowledge, eighteen cases have been reported to date. The present study reports three cases of PNET arising in the mesentery and ileocecum in 59- and 22-year-old males and a 36-year-old female. Computed tomography revealed a solid mass in the lower abdomen, with areas of cystic changes. Microscopically, the tumors were composed of small round cells arranged in sheets and rosettes with scant cytoplasm, hyperchromatic nuclei and a high mitotic rate. The tumor cells were immunopositive for CD99 and FLI1. EWS/FLI1 translocations were detected in all cases. Case 1 and case 2 underwent tumor resection without any preoperative radiotherapy, chemotherapy or biological therapy. Case 3 underwent tumor resection and received eight cycles of IAP chemotherapy (2.0 mg ifosfamide, 80 mg epirubicin, 30 mg cisplatin 30mg). Case 3 was followed up for 34 months until they succumbed to peritoneal recurrence, whereas the other cases were not followed up. The incidence of these small round-cell tumors in the intestinal system, their clinical and pathological features and differential diagnosis are discussed with a review of the literature.