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Oncogenic functions of the FOXC2 transcription factor: a hallmarks of cancer perspective

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Abstract

Epigenetic regulation of gene expression is a fundamental determinant of molecular and cellular function, and epigenetic reprogramming in the context of cancer has emerged as one of the key enabling characteristics associated with acquisition of the core hallmarks of this disease. As such, there has been renewed interest in studying the role of transcription factors as epigenetic regulators of gene expression in cancer. In this review, we discuss the current state of knowledge surrounding the oncogenic functions of FOXC2, a transcription factor that frequently becomes dysregulated in a variety of cancer types. In addition to highlighting the clinical impact of aberrant FOXC2 activity in cancer, we discuss mechanisms by which this transcription factor becomes dysregulated in both tumor and tumor-associated cells, placing particular emphasis on the ways in which FOXC2 promotes key hallmarks of cancer progression. Finally, we bring attention to important issues related to the oncogenic dysregulation of FOXC2 that must be addressed going forward in order to improve our understanding of FOXC2-mediated cancer progression and to guide prognostic and therapeutic applications of this knowledge in clinical settings.

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Funding

Work in the Hargadon lab is currently supported by a Mary Louise Andrews Award for Cancer Research from the Virginia Academy of Science. Portions of the figures in this review were generated using BioRender software.

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  1. Hargadon Laboratory, Department of Biology, Hampden-Sydney College, Hampden-Sydney, VA, 23943, USA

    Kristian M. Hargadon, Travis B. Goodloe III & Nathaniel D. Lloyd

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Kristian M. Hargadon—conceptualization, literature search, supervision, writing, and manuscript/figure preparation.

Travis B. Goodloe III—literature search, organization of data for tables.

Nathaniel D. Lloyd—literature search, organization of data for tables.

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Hargadon, K.M., Goodloe, T.B. & Lloyd, N.D. Oncogenic functions of the FOXC2 transcription factor: a hallmarks of cancer perspective. Cancer Metastasis Rev 41, 833–852 (2022). https://doi.org/10.1007/s10555-022-10045-3

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