Abstract
Forkhead box O transcription factors (FOXOs) regulate several signaling pathways and play crucial roles in health and disease. FOXOs are key regulators of the expression of genes involved in multiple cellular processes and their deregulation has been implicated in cancer. FOXOs are generally considered tumor suppressors and evidence also suggests that they may have a role in the regulation of cancer metabolism and angiogenesis. In order to continue growing and proliferating, tumor cells have to reprogram their metabolism and induce angiogenesis. Angiogenesis refers to the process of new blood capillary formation from pre-existing vessels, which is an essential driving force in cancer progression and metastasis through supplying tumor cells with oxygen and nutrients. This review summarizes the roles of FOXOs in the regulation of cancer metabolism and angiogenesis. A deeper knowledge of the involvement of FOXOs in these two key processes involved in cancer dissemination may help to develop novel therapeutic approaches for cancer treatment.
Highlights
Forkhead box O proteins (FOXOs) are a family of transcription factors that comprise a forkhead box (FOX) or winged helix conserved domain of 100 amino acid residues, which binds directly to various target sequences [1,2]
This review presents the most recent development regarding the role of FOXOs in cancer metabolism and angiogenesis
Increasing evidence supports a crucial role for FOXO proteins in cancer metabolism and angiogenesis
Summary
Forkhead box O proteins (FOXOs) are a family of transcription factors that comprise a forkhead box (FOX) or winged helix conserved domain of 100 amino acid residues, which binds directly to various target sequences [1,2]. FOXOs regulate cells differentiation, organ development, stem cell maintenance, and development [3,4,5]. They have a nuclear localization which can be transferred to the cytosol in the presence of growth factors, contributing to its degradation via ubiquitin proteosomal pathways. In the absence of growth factors, FOXOs translocate into the nucleus and regulate the expression of target genes involved in cell cycle arrest and apoptosis [6]. FOXOs are associated with many physiological and pathological processes, and are generally considered as tumor suppressors that retard cancer progression and inhibit metastasis by promoting apoptosis, DNA repair, cell cycle arrest, and oxidative stress resistance [10,11]. This review presents the most recent development regarding the role of FOXOs in cancer metabolism and angiogenesis
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