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Role of FoxO Proteins in Cellular Response to Antitumor Agents

Molecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(1), 90;
Received: 2 January 2019 / Revised: 8 January 2019 / Accepted: 10 January 2019 / Published: 14 January 2019
(This article belongs to the Special Issue Fox Proteins and Cancers: Old Proteins with Emerging New Tales)
PDF [1177 KB, uploaded 17 January 2019]


FoxO proteins (FoxOs) are transcription factors with a common DNA binding domain that confers selectivity for DNA interaction. In human cells, four proteins (FoxO1, FoxO3, FoxO4 and FoxO6), with redundant activity, exhibit mainly a positive effect on genes involved in cell cycle, apoptosis regulation and drug resistance. Thus, FoxOs can affect cell response to antitumor agent treatment. Their transcriptional activity depends on post-translational modifications, including phosphorylation, acetylation, and mono/poly-ubiquitination. Additionally, alterations in microRNA network impact on FoxO transcripts and in turn on FoxO levels. Reduced expression of FoxO1 has been associated with resistance to conventional agents (e.g., cisplatin) and with reduced efficacy of drug combinations in ovarian carcinoma cells. FoxO3 has been shown as a mediator of cisplatin toxicity in colorectal cancer. A requirement for FoxO3-induced apoptosis has been reported in cells exposed to targeted agents (e.g., gefitinib). Recently, the possibility to interfere with FoxO1 localization has been proposed as a valuable approach to improve cell sensitivity to cisplatin, because nuclear retention of FoxO1 may favor the induction of pro-apoptotic genes. This review focuses on the role of FoxOs in drug treatment response in tumor cells and discusses the impact of the expression of these transcription factors on drug resistance/sensitivity. View Full-Text
Keywords: FoxO; tumor; drug resistance FoxO; tumor; drug resistance

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Beretta, G.L.; Corno, C.; Zaffaroni, N.; Perego, P. Role of FoxO Proteins in Cellular Response to Antitumor Agents. Cancers 2019, 11, 90.

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