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

Lixia Gao, Liwei Lang, Xiangdong Zhao, Chloe Shay, Austin Y. Shull, Yong Teng

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2394-2404
Number of pages11
JournalOncogene
Volume38
Issue number13
DOIs
StatePublished - Mar 28 2019

Fingerprint

Fibroblast Growth Factor Receptors
Neoplasms
Autocrine Communication
Fibroblast Growth Factors
Gene Amplification
Growth
Carcinoma, squamous cell of head and neck
Agar
Cell Proliferation
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

FGF19 amplification reveals an oncogenic dependency upon autocrine FGF19/FGFR4 signaling in head and neck squamous cell carcinoma. / Gao, Lixia; Lang, Liwei; Zhao, Xiangdong; Shay, Chloe; Shull, Austin Y.; Teng, Yong.

In: Oncogene, Vol. 38, No. 13, 28.03.2019, p. 2394-2404.

Research output: Contribution to journalArticle

Gao, Lixia ; Lang, Liwei ; Zhao, Xiangdong ; Shay, Chloe ; Shull, Austin Y. ; Teng, Yong. / FGF19 amplification reveals an oncogenic dependency upon autocrine FGF19/FGFR4 signaling in head and neck squamous cell carcinoma. In: Oncogene. 2019 ; Vol. 38, No. 13. pp. 2394-2404.
@article{59c4d9a3cb1f491d8642ba77c0d3d8f2,
title = "FGF19 amplification reveals an oncogenic dependency upon autocrine FGF19/FGFR4 signaling in head and neck squamous cell carcinoma",
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.",
author = "Lixia Gao and Liwei Lang and Xiangdong Zhao and Chloe Shay and Shull, {Austin Y.} and Yong Teng",
year = "2019",
month = "3",
day = "28",
doi = "10.1038/s41388-018-0591-7",
language = "English (US)",
volume = "38",
pages = "2394--2404",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "13",

}

TY - JOUR

T1 - FGF19 amplification reveals an oncogenic dependency upon autocrine FGF19/FGFR4 signaling in head and neck squamous cell carcinoma

AU - Gao, Lixia

AU - Lang, Liwei

AU - Zhao, Xiangdong

AU - Shay, Chloe

AU - Shull, Austin Y.

AU - Teng, Yong

PY - 2019/3/28

Y1 - 2019/3/28

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85058036399&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058036399&partnerID=8YFLogxK

U2 - 10.1038/s41388-018-0591-7

DO - 10.1038/s41388-018-0591-7

M3 - Article

VL - 38

SP - 2394

EP - 2404

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 13

ER -