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Springer Science and Business Media LLC Cell Death & Disease 17(1)
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    초록·키워드

    FOXM1 (forkhead box protein M1) is a member of the transcription factors (TF) in the forkhead (FOX) family. Numerous studies over the past several years have progressively contributed to our current understanding of FOXM1 functions. Early work characterized FOXM1 as a proliferation-associated mammalian TF that controls cell cycle-transcriptional program, and is essential for proper mitotic function and genomic stability in normal cells. However, FOXM1 is aberrantly high-expressed in the majority of human cancers. A large body of literature from different studies has demonstrated FOXM1 as a critical molecule that regulates multiple aspects of cancer cells and maintains all major cancer hallmarks. In addition, recent studies have documented FOXM1 in cancer therapy resistance. Indeed, FOXM1 is repeatedly identified as a common factor associated with the higher cancer stage and weaker response to cancer therapies by regulating several targets relevant to drug response and cell survival. FOXM1-dependent transcriptional activity and downstream pathways regulate multiple functions in response to drug-induced genotoxic stress, oxidative stress, and mitotic catastrophe. FOXM1 also interacts with other proteins, and these protein-protein interactions regulate different functions and signaling pathways in response to drug-induced toxicity. Here, we mainly review and discuss our current molecular understanding of the mechanisms through which FOXM1 in cancer cells executes these new roles, and thereby induces therapy resistance and inhibits apoptosis in a variety of human cancers. We also discuss the opportunity and challenges for therapeutically targeting FOXM1 to induce apoptosis in drug-resistant cancers.

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