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The FOXO family of transcription factors: key molecular players in gastric cancer

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Abstract

Gastric cancer (GC) is the fifth most frequently diagnosed cancer worldwide and the third leading cause of cancer-related death with an oncological origin. Despite its decline in incidence and mortality in recent years, GC remains a global public problem that seriously threatens patients’ health and lives. The forkhead box O proteins (FOXOs) are a family of evolutionarily conserved transcription factors (TFs) with crucial roles in cell fate decisions. In mammals, the FOXO family consists of four members FOXO1, 3a, 4, and 6. FOXOs play crucial roles in a variety of biological processes, such as development, metabolism, and stem cell maintenance, by regulating the expression of their target genes in space and time. An accumulating amount of evidence has shown that the dysregulation of FOXOs is involved in GC progression by affecting multiple cellular processes, including proliferation, apoptosis, invasion, metastasis, cell cycle progression, carcinogenesis, and resistance to chemotherapeutic drugs. In this review, we systematically summarize the recent findings on the regulatory mechanisms of FOXO family expression and activity and elucidate its roles in GC progression. Moreover, we also highlight the clinical implications of FOXOs in GC treatment.

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Funding

All authors are supported by Qingdao Medical College, Qingdao University. This work was supported by the National Natural Science Foundation of China (81802822) and the China Postdoctoral Science Foundation (2018M642607).

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Authors and Affiliations

  1. Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao Medical College, Qingdao University, Qingdao, 266021, China

    Ying Liu & Jianxun Wang

  2. School of Basic Medical Sciences, Qingdao Medical College, Qingdao University, Qingdao, 266071, China

    Ying Liu, Xiang Ao, Yi Jia, Xiaoge Li, Yu Wang & Jianxun Wang

Authors
  1. Ying Liu
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  2. Xiang Ao
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  3. Yi Jia
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  4. Xiaoge Li
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  5. Yu Wang
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  6. Jianxun Wang
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Contributions

Ying Liu: writing–conceptualization, original draft preparation, writing–review and editing. Xiang Ao: data curation, funding acquisition. Yi Jia: data curation. Xiaoge Li: data curation. Yu Wang: data curation. Jianxun Wang: review and editing.

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Correspondence to Ying Liu.

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Liu, Y., Ao, X., Jia, Y. et al. The FOXO family of transcription factors: key molecular players in gastric cancer. J Mol Med 100, 997–1015 (2022). https://doi.org/10.1007/s00109-022-02219-x

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  • DOI: https://doi.org/10.1007/s00109-022-02219-x

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