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

33 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
Externally publishedYes

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