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Multiple roles of HOX proteins in Metastasis: Let me count the ways

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Abstract

Knowledge of the role of HOX proteins in cancer has been steadily accumulating in the last 25 years. They are encoded by 39 HOX genes arranged in 4 distinct clusters, and have unique and redundant function in all types of cancers. Many HOX genes behave as oncogenic transcriptional factors regulating multiple pathways that are critical to malignant progression in a variety of tumors. Some HOX proteins have dual roles that are tumor-site specific, displaying both oncogenic and tumor suppressor function. The focus of this review is on how HOX proteins contribute to growth or suppression of metastasis. The review will cover HOX protein function in the critical aspects of epithelial-mesenchymal transition, in cancer stem cell sustenance and in therapy resistance, manifested as distant metastasis. The emerging role of adiposity in both initiation and progression of metastasis is described. Defining the role of HOX genes in the metastatic process has identified candidates for targeted cancer therapies that may combat the metastatic process. We will discuss potential therapeutic opportunities, particularly in pathways influenced by HOX proteins.

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Supported by the Rubenstein Family Funds, and the AVON Foundation for Cancer Research.

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  1. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, 1650 Orleans Street, CRB1-143, Baltimore, MD, 21231, USA

    Joy Jonkers, Priya Pai & Saraswati Sukumar

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The review was written by SS, reviewed and edited by JJ and PP. The figures were prepared by JJ and PP.

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Jonkers, J., Pai, P. & Sukumar, S. Multiple roles of HOX proteins in Metastasis: Let me count the ways. Cancer Metastasis Rev 39, 661–679 (2020). https://doi.org/10.1007/s10555-020-09908-4

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