LIN28B promotes neuroblastoma metastasis and regulates PDZ binding kinase.

LIN28B promotes neuroblastoma metastasis and regulates PDZ binding kinase. Neoplasia. 2020 Apr 24;22(6):231-241 Authors: Chen D, Cox J, Annam J, Weingart M, Essien G, Rathi KS, Rokita JL, Khurana P, Cuya SM, Bosse KR, Pilgrim A, Li D, Shields C, Laur O, Maris JM, Schnepp RW Abstract Neuroblastoma is an aggressive pediatric malignancy of the neural crest with suboptimal cure rates and a striking predilection for widespread metastases, underscoring the need to identify novel therapeutic vulnerabilities. We recently identified the RNA binding protein LIN28B as a driver in high-risk neuroblastoma and demonstrated it promotes oncogenic cell proliferation by coordinating a RAN-Aurora kinase A network. Here, we demonstrate that LIN28B influences another key hallmark of cancer, metastatic dissemination. Using a murine xenograft model of neuroblastoma dissemination, we show that LIN28B promotes metastasis. We demonstrate that this is in part due to the effects of LIN28B on self-renewal and migration, providing an understanding of how LIN28B shapes the metastatic phenotype. Our studies reveal that the let-7 family, which LIN28B inhibits, decreases self-renewal and migration. Next, we identify PDZ Binding Kinase (PBK) as a novel LIN28B target. PBK is a serine/threonine kinase that promotes the proliferation and self-renewal of neural stem cells and serves as an oncogenic driver in multiple aggressive malignancies. We demonstrate that PBK is bot...
Source: Neoplasia - Category: Cancer & Oncology Authors: Tags: Neoplasia Source Type: research