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Partial EMT in head and neck cancer biology: a spectrum instead of a switch

Oncogene volume 40, pages 5049–5065 (2021)Cite this article

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Abstract

Our understanding of epithelial-to-mesenchymal transition (EMT) has slowly evolved from a simple two state, binary model to a multi-step, dynamic continuum of epithelial-to-mesenchymal plasticity, with metastable intermediate transition states that may drive cancer metastasis. Head and neck cancer is no exception, and in this review, we use head and neck as a case study for how partial-EMT (p-EMT) cell states may play an important role in cancer progression. In particular, we summarize recent in vitro and in vivo studies that uncover these intermediate transition states, which exhibit both epithelial and mesenchymal properties and appear to have distinct advantages in migration, survival in the bloodstream, and seeding and propagation within secondary metastatic sites. We then summarize the common and distinct regulators of p-EMT as well as methodologies for identifying this unique cellular subpopulation, with a specific emphasis on the role of cutting-edge technologies, such as single cell approaches. Finally, we propose strategies to target p-EMT cells, highlighting potential opportunities for therapeutic intervention to specifically target the process of metastasis. Thus, although significant challenges remain, including numerous gaps in current knowledge, a deeper understanding of EMT plasticity and a genuine identification of EMT as spectrum rather than a switch will be critical for improving patient diagnosis and treatment across oncology.

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Fig. 1: Partial-EMT (p-EMT) cells in cancer progression.
Fig. 2: In vivo detection of partial EMT cells.
Fig. 3: Energy model of EMT transition states.
Fig. 4: Partial EMT cells at the leading edge of the tumor are prone to collective migration and CTC cluster formation with increased metastatic rate.

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Acknowledgements

This work was graciously supported by an NIH/NCI K08CA237732 as well as the Cancer Research Foundation: P20-0563, Doris Duke Foundation, American Cancer Society, V Foundation: V2019-005, and the Washington University Dean’s Scholars Program (SVP). This work was also supported by the National Institute of Deafness and Other Communication Disorders (T32DC000022) (TFB).

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  1. These authors contributed equally: Ananya Pal, Thomas F Barrett.

Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA

    Ananya Pal, Thomas F. Barrett, Rachel Paolini & Sidharth V. Puram

  2. Department of Otolaryngology-Head and Neck Surgery, Columbia University Vagelos College of Physicians & Surgeons, New York, NY, USA

    Anuraag Parikh

  3. Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA

    Sidharth V. Puram

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  1. Ananya Pal
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Pal, A., Barrett, T.F., Paolini, R. et al. Partial EMT in head and neck cancer biology: a spectrum instead of a switch. Oncogene 40, 5049–5065 (2021). https://doi.org/10.1038/s41388-021-01868-5

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