Ovarian cancer (OC), one of the three most common gynecological malignancies, is characterized by low early detection rates and poor prognosis. Patients with OC face a high risk of developing transcoelomic metastasis\u2014the spread of cancer cells within the abdominal cavity\u2014during the early stages of the disease, a process strongly linked to poor survival outcomes. However, the underlying mechanisms of how OC cells spread from the primary tumor to distant sites have remained elusive.<\/p>\n
In a recent study published in Genes & Diseases, researchers from Tianjin Medical University, Tianjin Central Hospital of Gynecology Obstetrics, and Nankai University, employed CRISPR-based large-scale genetic screening alongside an orthotopic ovarian cancer mouse model with gene knockout cells to unravel the molecular mechanisms underlying OC.<\/p>\n
Using a genome-wide in vivo CRISPR\/Cas9 screening approach combined with patient-derived transcriptomic datasets, researchers identified neuroblastoma suppressor of tumorigenicity 1 (NBL1) as one of the most critical genes promoting transcoelomic metastasis<\/a>. NBL1 was found to be significantly overexpressed in metastatic ovarian tumors, with expression levels strongly correlating with advanced clinical stage and poor survival outcomes.<\/p>\n Further experiments by the team revealed that NBL1 promotes OC cell proliferation, migration, invasion, and resistance to apoptosis through dual mechanisms: i) direct activation of Jak\/Stat3 signaling via physical interaction and ii) suppression of anti-tumor immunity by limiting T cell<\/a> infiltration. Notably, the Stat3 inhibitor Wp1066 was shown to block NBL1-driven metastasis, reversing its effects on cell proliferation, migration, and epithelial-mesenchymal transition (EMT), both in in vitro and in vivo models.<\/p>\n In conclusion, this study reveals a previously unrecognized oncogenic role of NBL1 in OC metastasis through Jak\/Stat3 pathway activation. Its strong association with poor prognosis, combined with reversibility by Stat3 inhibitors, positions NBL1 as both a prognostic biomarker<\/a> and a promising therapeutic target.<\/p>\n Source:<\/p>\n Journal reference:<\/p>\n