Colon cancer progression is driven by APEX1-mediated upregulation of Jagged

Mi Hwa Kim, Hong Beum Kim, Sang Pil Yoon, Sung Chul Lim, Man Jin Cha, Young Jin Jeon, Sang Gon Park, In Youb Chang, Ho Jin You

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3211-3230
Number of pages20
JournalJournal of Clinical Investigation
Volume123
Issue number8
DOIs
StatePublished - Aug 1 2013

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