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FGF19 amplification reveals an oncogenic dependency upon autocrine FGF19/FGFR4 signaling in head and neck squamous cell carcinoma

Oncogene volume 38, pages 2394–2404 (2019)Cite this article

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Abstract

The fibroblast growth factor 19 gene FGF19 has previously been reported to be amplified in several cancer types and encodes for a key autocrine signaler known to promote tumorigenic growth. Thus, it is imperative to understand which cancers are oncogenically addicted to FGF19 amplification as well as the role it serves in these cancer types. We report for the first time high FGF19 amplification in head and neck squamous cell carcinomas (HNSCC), which is associated with increased autocrine secretion of FGF19 and poor patient outcome in HNSCC. FGF19 amplification corresponded with constitutive activation of FGF receptor 4 (FGFR4)-dependent ERK/AKT–p70S6K–S6 signaling activation in HNSCC cells, and addition of human recombinant FGF19 could promote cell proliferation and soft agar colony formation in HNSCC cells with low FGF19 expression through activation of FGFR4 and downstream signaling cascades. In contrast, FGF19 knockout counteracts the observed effects in HNSCC cells carrying high endogenous FGF19, with knockout of FGF19 significantly suppressing tumor growth in an orthotopic mouse model of HNSCC. Collectively, this study demonstrates that FGF19 gene amplification corresponds with an increased dependency upon FGF19/FGFR4 autocrine signaling in HNSCC, revealing a therapeutic target for this cancer type.

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Acknowledgements

This work was supported in part by Dental College of Georgia Special Funding Initiative and a grant from the Department of Defense (W81XWH-14-1-0412) (to Y.T.). The authors sincerely thank Dr. Andrew W. Yeudall (Augusta University) for providing HNSCC cells for this study.

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    Authors and Affiliations

    1. Department of Oral Biology and Diagnostic Sciences, Augusta University, Augusta, GA, USA

      Lixia Gao, Liwei Lang, Xiangdong Zhao & Yong Teng

    2. Emory Children’s Center, Emory University, Atlanta, GA, USA

      Chloe Shay

    3. Department of Biology, Presbyterian College, Clinton, SC, USA

      Austin Y. Shull

    4. Georgia Cancer Center, Augusta University, Augusta, GA, USA

      Yong Teng

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    1. Lixia Gao
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    Correspondence to Yong Teng.

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    These authors contributed equally: Lixia Gao, Liwei Lang

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    Gao, L., Lang, L., Zhao, X. et al. FGF19 amplification reveals an oncogenic dependency upon autocrine FGF19/FGFR4 signaling in head and neck squamous cell carcinoma. Oncogene 38, 2394–2404 (2019). https://doi.org/10.1038/s41388-018-0591-7

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