title: Epsin Family of Endocytic Adaptor Proteins as Oncogenic Regulators of Cancer Progression.
abstract: Tumor angiogenesis, tumor cell proliferation, and tumor cell migration result from an accumulation of oncogenic mutations that alter protein expression and the regulation of various signaling cascades. Epsins, a small family of clathrin-mediated endocytic adaptor proteins, are reportedly upregulated in a variety of cancers. Importantly, loss of epsins protects against tumorigenesis, thus supporting an oncogenic role for epsins in cancer. Although a clear relationship between epsins and cancer has evolved, the importance of this relationship with regards to cancer progression and anti-cancer therapies remains unclear. In this review, we summarize epsins' role as endocytic adaptors that modulate VEGF and Notch signaling through the regulated internalization of VEGFR2 and trans-endocytosis of Notch receptors. As both VEGF and Notch signaling have significant implications in angiogenesis, we focus on the newly identified role for epsins in tumor angiogenesis. In addition to epsins' canonical role in receptor-mediated endocytosis, and the resulting downstream signaling regulation, we discuss the non-canonical role of epsins as regulators of small GTPases and the implications this has on tumor cell proliferation and invasion. Given epsins' identified roles in tumor angiogenesis, tumor cell proliferation, and tumor cell invasion, we predict that the investigative links between epsins and cancer will provide new insights into the importance of endocytic adaptors and their potential use as future therapeutic targets.
authors: Cardiovascular Biology Program, Oklahoma Medical Research Foundation, 825 N.E. 13 Street, Oklahoma City, OK 73104, USA.
authors: Kandice L
authors: KL
authors: Tessneer
authors: Cardiovascular Biology Program, Oklahoma Medical Research Foundation, 825 N.E. 13 Street, Oklahoma City, OK 73104, USA.
authors: Xiaofeng
authors: X
authors: Cai
authors: Cardiovascular Biology Program, Oklahoma Medical Research Foundation, 825 N.E. 13 Street, Oklahoma City, OK 73104, USA.
authors: Satish
authors: S
authors: Pasula
authors: Cardiovascular Biology Program, Oklahoma Medical Research Foundation, 825 N.E. 13 Street, Oklahoma City, OK 73104, USA.
authors: Yunzhou
authors: Y
authors: Dong
authors: Cardiovascular Biology Program, Oklahoma Medical Research Foundation, 825 N.E. 13 Street, Oklahoma City, OK 73104, USA ; Biochemistry and Molecular Biology Department, University of Oklahoma Health Science Center, 940 Stanton L. Young Blvd., Oklahoma City, OK 73104, USA.
authors: Xiaolei
authors: X
authors: Liu
authors: Cardiovascular Biology Program, Oklahoma Medical Research Foundation, 825 N.E. 13 Street, Oklahoma City, OK 73104, USA.
authors: Baojun
authors: B
authors: Chang
authors: Cardiovascular Biology Program, Oklahoma Medical Research Foundation, 825 N.E. 13 Street, Oklahoma City, OK 73104, USA.
authors: John
authors: J
authors: McManus
authors: Cardiovascular Biology Program, Oklahoma Medical Research Foundation, 825 N.E. 13 Street, Oklahoma City, OK 73104, USA.
authors: Scott
authors: S
authors: Hahn
authors: Cardiovascular Biology Program, Oklahoma Medical Research Foundation, 825 N.E. 13 Street, Oklahoma City, OK 73104, USA.
authors: Lili
authors: L
authors: Yu
authors: Cardiovascular Biology Program, Oklahoma Medical Research Foundation, 825 N.E. 13 Street, Oklahoma City, OK 73104, USA ; Biochemistry and Molecular Biology Department, University of Oklahoma Health Science Center, 940 Stanton L. Young Blvd., Oklahoma City, OK 73104, USA.
authors: Hong
authors: H
authors: Chen
keywords: Angiogenesis; Cancer; Epsin; Notch; VEGF