250 Sub-cellular expression of Ape1/Ref1 in hepatocellular carcinoma at different stages: Possible prognostic significance

Maso, Victor; Crocè, Lory Saveria; Avellini, Chiara; Tell, Gianluca; Mistro, V. Del; Intini, S; Cattin, Elisa; Sasso, Elizabeth B.; Tiribelli, Claudio

doi:10.1016/s0168-8278(06)80251-5

Cited by 4 publications

(5 citation statements)

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“…Accumulating evidence indicates that aberrant APEX1 expression is a general phenomenon in human cancers (18,(21)(22)(23)(24)(25). Although previous studies suggested the involvement of APEX1 in tumor progression, its exact role in tumorigenicity remained elusive.…”

Section: Discussionmentioning

confidence: 99%

“…It also stimulates the DNA-binding activity of a number of transcription factors involved in cancer promotion and progression, such as AP1, NF-κB, p53, early growth response 1 (EGR1), MYB, HLF, and PAX8 (14,15). APEX1 is often overexpressed in solid tumors (16)(17)(18)(19)(20)(21), and its expression level and subcellular localization have been related to clinical stage and poor prognosis in various tumors, including breast cancer, cervical cancer, colorectal cancer, hepatic cancer, prostate cancer, and osteosarcoma (18,(21)(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

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

Kim

Yoon

et al. 2013

J. Clin. Invest.

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Kim

Yoon

et al. 2013

J. Clin. Invest.

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“…Several human cancers, including lung (Kakolyris et al, 1999;Puglisi et al, 2001), prostate (Kelly, 2000), cervical (Xu et al, 1997), ovarian (Moore et al, 2000;Freitas et al, 2003), breast (Puglisi et al, 2002) and hepatocellular (Di Maso et al, 2007) carcinomas, have been reported to have poorer prognosis in patients' tumor, with cytoplasmic and/or nuclear localization of Ape1. However, the causal role of cytoplasmic localization of Ape1 on lung tumor malignancy is yet to be elucidated .…”

Section: Introductionmentioning

confidence: 99%

Subcellular localization of apurinic endonuclease 1 promotes lung tumor aggressiveness via NF-κB activation

Cheng

Chang

et al. 2010

Oncogene

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Apurinic endonuclease 1 (Ape1) is not only involved in base excision repair, but also activates some transcriptional factors through its redox activity. However, which subcellular localization of Ape1 is involved in the activation of transcriptional factor remains unclear. We first observed that Cox-2 expression was associated with cytoplasmic Ape1 expression in lung tumors and cancer cell lines. We thus hypothesize that nuclear factor (NF)-jB is activated by cytoplasmic Ape1 to cause Cox-2 expression. Herein, we generated cytoplasmic and nuclear Ape1 in Ape1-knockdown lung cancer cells by exogenous expression of Ape1 containing various deletions and/or mutations of the nuclear localization sequence. It was observed that cytoplasmic Ape1, but not nuclear Ape1, induced Cox-2 expression through NF-jB activation. NF-jB activation by cytoplasmic Ape1 was diminished by the Ape1 redox activity inhibitor resveratrol. Cells expressing cytoplasmic Ape1 exhibited tumor progression and metastasis in vitro and in vivo as xenografts, but cells expressing nuclear Ape1 did not. Patients with tumors containing elevated cytoplasmic Ape1 had a poor prognosis and a 3.722-fold risk of tumor recurrence and/or metastasis. Cytoplasmic Ape1 could therefore enhance lung tumor malignancy through NF-jB activation, suggesting that combination of cisplatin and specific redox inhibitor could improve chemotherapeutic response in patients with tumors containing elevated cytoplasmic Ape1.

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“…In both adenomas and carcinomas, subcellular restriction is lost and a mixed localisation pattern develops, with a predominance of cytoplasmic staining (Kakolyris et al 1997). Increased cytoplasmic staining is also seen in thyroid (Tell et al 2000), hepatocellular (Di Maso et al 2007), epithelial ovarian (Moore et al 2000) and prostate carcinomas . In contrast, melanomas display an increased level of APE1 expression which is predominantly localised to the nucleus, compared to cytoplasmic staining in normal skin (Yang et al 2005).…”

Section: Ape1 and Human Cancermentioning

confidence: 99%