title: Colon cancer progression is driven by APEX1-mediated upregulation of Jagged.
abstract: Aberrant expression of apurinic-apyrimidinic endonuclease-1 (APEX1) has been reported in numerous human solid tumors and is positively correlated with cancer progression; however, the role of APEX1 in tumor progression is poorly defined. Here, we show that APEX1 contributes to aggressive colon cancer behavior and functions as an upstream activator in the Jagged1/Notch signaling pathway. APEX1 overexpression or knockdown in human colon cancer cell lines induced profound changes in malignant properties such as cell proliferation, anchorage-independent growth, migration, invasion, and angiogenesis in vitro and in tumor formation and metastasis in mouse xenograft models. These oncogenic effects of APEX1 were mediated by the upregulation of Jagged1, a major Notch ligand. Furthermore, APEX1 expression was associated with Jagged1 in various colon cancer cell lines and in tissues from colon cancer patients. This finding identifies APEX1 as a positive regulator of Jagged1/Notch activity and suggests that it is a potential therapeutic target in colon cancers that exhibit high levels of Jagged1/Notch signaling.
authors.forename: Mi-Hwa
authors.initials: MH
authors.lastname: Kim
authors.forename: Hong-Beum
authors.initials: HB
authors.lastname: Kim
authors.forename: Sang Pil
authors.initials: SP
authors.lastname: Yoon
authors.forename: Sung-Chul
authors.initials: SC
authors.lastname: Lim
authors.forename: Man Jin
authors.initials: MJ
authors.lastname: Cha
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Sang Gon
authors.initials: SG
authors.lastname: Park
authors.forename: In-Youb
authors.initials: IY
authors.lastname: Chang
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: You