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The APE1/REF-1 and the hallmarks of cancer

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Abstract

APE1/REF-1 (apurinic/apyrimidinic endonuclease 1 / redox factor-1) is a protein with two domains, with endonuclease function and redox activity. Its main activity described is acting in DNA repair by base excision repair (BER) pathway, which restores DNA damage caused by oxidation, alkylation, and single-strand breaks. In contrast, the APE1 redox domain is responsible for regulating transcription factors, such as AP-1 (activating protein-1), NF-κB (Nuclear Factor kappa B), HIF-1α (Hypoxia-inducible factor 1-alpha), and STAT3 (Signal Transducers and Activators of Transcription 3). These factors are involved in physiological cellular processes, such as cell growth, inflammation, and angiogenesis, as well as in cancer. In human malignant tumors, APE1 overexpression is associated with lung, colon, ovaries, prostate, and breast cancer progression, more aggressive tumor phenotypes, and worse prognosis. In this review, we explore APE1 and its domain’s role in cancer development processes, highlighting the role of APE1 in the hallmarks of cancer. We reviewed original articles and reviews from Pubmed related to APE1 and cancer and found that both domains of APE1/REF-1, but mainly its redox activity, are essential to cancer cells. This protein is often overexpressed in cancer, and its expression and activity are correlated to processes such as proliferation, invasion, inflammation, angiogenesis, and resistance to cell death. Therefore, APE1 participates in essential processes of cancer development. Then, the activity of APE1/REF-1 in these hallmarks suggests that targeting this protein could be a good therapeutic approach.

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Acknowledgements

We thank Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Conselho Nacional de Desenvolvimento Científico e Tecnológico and Programa de pós-graduação em Biociências/Pró-reitoria de extensão, for financial support.

Funding

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Programa de pós-graduação em Biociências (PPGB) e Pró-reitoria de extensão through CNPq funding.

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  1. Priscyanne Barreto Siqueira and Mariana Moreno de Sousa Rodrigues contributed equally to this article.

Authors and Affiliations

  1. Departamento de Biofísica e Biometria, Laboratório de Biologia do Câncer, Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcântara Gomes, Rio de Janeiro, Brasil

    Priscyanne Barreto Siqueira, Mariana Moreno de Sousa Rodrigues, Ísis Salviano Soares de Amorim, Matheus da Silva Oliveira, Juliana Alves Rodrigues & Andre Luiz Mencalha

  2. Laboratório de Alimentos Funcionais, Universidade Federal do Rio de Janeiro, Instituto de Nutrição Josué de Castro, Rio de Janeiro, Brasil

    Ísis Salviano Soares de Amorim

  3. Departamento de Biofísica e Biometria, Laboratório de Biofotônica, Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcântara Gomes, Rio de Janeiro, Brasil

    Thayssa Gomes da Silva & Adenilson de Souza da Fonseca

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Contributions

PBS, MMSR, ISSA, TGS, MSO, and JAR performed the literature search and drafted the manuscript. PBS and MMSR prepared Figs. 1 and 2. PBS, MMSR, ISSA, and TGS prepared the Table 1. ASF and ALM revised the work.

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Correspondence to Priscyanne Barreto Siqueira or Mariana Moreno de Sousa Rodrigues.

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Siqueira, P.B., de Sousa Rodrigues, M.M., de Amorim, Í.S.S. et al. The APE1/REF-1 and the hallmarks of cancer. Mol Biol Rep 51, 47 (2024). https://doi.org/10.1007/s11033-023-08946-9

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