title: Endocytic adaptor protein epsin is elevated in prostate cancer and required for cancer progression.
abstract: Epsins have an important role in mediating clathrin-mediated endocytosis of ubiquitinated cell surface receptors. The potential role for epsins in tumorigenesis and cancer metastasis by regulating intracellular signaling pathways has largely not been explored. Epsins are reportedly upregulated in several types of cancer including human skin, lung, and canine mammary cancers. However, whether their expression is elevated in prostate cancer is unknown. In this study, we investigated the potential role of epsins in prostate tumorigenesis using the wild type or epsin-deficient human prostate cancer cells, LNCaP, in a human xenograft model, and the spontaneous TRAMP mouse model in wild type or epsin-deficient background. Here, we reported that the expression of epsins 1 and 2 is upregulated in both human and mouse prostate cancer cells and cancerous tissues. Consistent with upregulation of epsins in prostate tumors, we discovered that depletion of epsins impaired tumor growth in both the human LNCaP xenograft and the TRAMP mouse prostate. Furthermore, epsin depletion significantly prolonged survival in the TRAMP mouse model. In summary, our findings suggest that epsins may act as oncogenic proteins to promote prostate tumorigenesis and that depletion or inhibition of epsins may provide a novel therapeutic target for future prostate cancer therapies.
authors.affiliation: Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors.forename: Kandice L
authors.initials: KL
authors.lastname: Tessneer
authors.forename: Satish
authors.initials: S
authors.lastname: Pasula
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Cai
authors.forename: Yunzhou
authors.initials: Y
authors.lastname: Dong
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Liu
authors.forename: Lili
authors.initials: L
authors.lastname: Yu
authors.forename: Scott
authors.initials: S
authors.lastname: Hahn
authors.forename: John
authors.initials: J
authors.lastname: McManus
authors.forename: Yiyuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Baojun
authors.initials: B
authors.lastname: Chang
authors.forename: Hong
authors.initials: H
authors.lastname: Chen