PDF(Pubmed)
Abstract：
Adhesion to and clearance of the mesothelial monolayer are key early events in metastatic seeding of ovarian cancer. ROR2 is a receptor tyrosine kinase that interacts with Wnt5a ligand to activate noncanonical Wnt signaling and has been previously shown to be upregulated in ovarian cancer tissue. However, no prior study has evaluated the mechanistic role of ROR2 in ovarian cancer. Through a cellular high-throughput genetic screen, we independently identified ROR2 as a driver of ovarian tumor cell adhesion and invasion. ROR2 expression in ovarian tumor cells serves to drive directed cell migration preferentially toward areas of high Wnt5a ligand, such as the mesothelial lined omentum. In addition, ROR2 promotes ovarian tumor cell adhesion and clearance of a mesothelial monolayer. Depletion of ROR2, in tumor cells, reduces metastatic tumor burden in a syngeneic model of ovarian cancer. These findings support the role of ROR2 in ovarian tumor cells as a critical factor contributing to the early steps of metastasis. Therapeutic targeting of the ROR2/Wnt5a signaling axis could provide a means of improving treatment for patients with advanced ovarian cancer.
UNASSIGNED: This study demonstrates that ROR2 in ovarian cancer cells is important for directed migration to the metastatic niche and provides a potential signaling axis of interest for therapeutic targeting in ovarian cancer.
UNASSIGNED: This study demonstrates that ROR2 in ovarian cancer cells is important for directed migration to the metastatic niche and provides a potential signaling axis of interest for therapeutic targeting in ovarian cancer.
摘要：
间皮单层的粘附和清除是卵巢癌转移种植的关键早期事件。ROR2是与Wnt5a配体相互作用以激活非经典Wnt信号传导的受体酪氨酸激酶,并且先前已显示在卵巢癌组织中上调。然而,之前没有研究评估ROR2在卵巢癌中的作用机制.通过细胞高通量遗传筛选，我们独立确定ROR2是卵巢肿瘤细胞粘附和侵袭的驱动因素.ROR2在卵巢肿瘤细胞中的表达用于驱动定向细胞优先向高Wnt5a配体区域迁移，如间皮衬里网膜。此外,ROR2促进卵巢肿瘤细胞粘附和间皮单层的清除。肿瘤细胞中ROR2的耗尽，减少同系卵巢癌模型中的转移性肿瘤负担。这些发现支持ROR2在卵巢肿瘤细胞中作为促成早期转移的关键因素的作用。ROR2/Wnt5a信号轴的治疗靶向可以提供改善晚期卵巢癌患者治疗的手段。含义：这项研究表明，卵巢癌细胞中的ROR2对于定向迁移到转移性生态位很重要，并为卵巢癌的治疗靶向提供了潜在的目标信号轴。
