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Fibroblast growth factor receptor 4 regulates tumor invasion by coupling fibroblast growth factor signaling to extracellular matrix degradation

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Harvard

Sugiyama, N, Varjosalo, M, Meller, P, Lohi, J, Hyytiäinen, M, Kilpinen, S, Kallioniemi, O, Ingvarsen, S, Engelholm, LH, Taipale, J, Alitalo, K, Keski-Oja, J & Lehti, K 2010, 'Fibroblast growth factor receptor 4 regulates tumor invasion by coupling fibroblast growth factor signaling to extracellular matrix degradation' Cancer Research, bind 70, nr. 20, s. 7851-61. https://doi.org/10.1158/0008-5472.CAN-10-1223

APA

CBE

Sugiyama N, Varjosalo M, Meller P, Lohi J, Hyytiäinen M, Kilpinen S, Kallioniemi O, Ingvarsen S, Engelholm LH, Taipale J, Alitalo K, Keski-Oja J, Lehti K. 2010. Fibroblast growth factor receptor 4 regulates tumor invasion by coupling fibroblast growth factor signaling to extracellular matrix degradation. Cancer Research. 70(20):7851-61. https://doi.org/10.1158/0008-5472.CAN-10-1223

MLA

Vancouver

Author

Sugiyama, Nami ; Varjosalo, Markku ; Meller, Pipsa ; Lohi, Jouko ; Hyytiäinen, Marko ; Kilpinen, Sami ; Kallioniemi, Olli ; Ingvarsen, Signe ; Engelholm, Lars H ; Taipale, Jussi ; Alitalo, Kari ; Keski-Oja, Jorma ; Lehti, Kaisa. / Fibroblast growth factor receptor 4 regulates tumor invasion by coupling fibroblast growth factor signaling to extracellular matrix degradation. I: Cancer Research. 2010 ; Bind 70, Nr. 20. s. 7851-61.

Bibtex

@article{23bc1f7db97f444ab33ad190769f1d50,
title = "Fibroblast growth factor receptor 4 regulates tumor invasion by coupling fibroblast growth factor signaling to extracellular matrix degradation",
abstract = "Aberrant expression and polymorphism of fibroblast growth factor receptor 4 (FGFR4) has been linked to tumor progression and anticancer drug resistance. We describe here a novel mechanism of tumor progression by matrix degradation involving epithelial-to-mesenchymal transition in response to membrane-type 1 matrix metalloproteinase (MT1-MMP, MMP-14) induction at the edge of tumors expressing the FGFR4-R388 risk variant. Both FGFR4 and MT1-MMP were upregulated in tissue biopsies from several human cancer types including breast adenocarcinomas, where they were partially coexpressed at the tumor/stroma border and tumor invasion front. The strongest overall coexpression was found in prostate carcinoma. Studies with cultured prostate carcinoma cell lines showed that the FGFR4-R388 variant, which has previously been associated with poor cancer prognosis, increased MT1-MMP-dependent collagen invasion. In this experimental model, knockdown of FGFR4-R388 or MT1-MMP by RNA interference blocked tumor cell invasion and growth in collagen. This was coupled with impaired phosphorylation of FGFR substrate 2 and Src, upregulation of E-cadherin, and suppression of cadherin-11 and N-cadherin. These in vitro results were substantiated by reduced MT1-MMP content and in vivo growth of prostate carcinoma cells after the FGFR4-R388 gene silencing. In contrast, knockdown of the alternative FGFR4-G388 allele enhanced MT1-MMP and invasive tumor cell growth in vivo and within three-dimensional collagen. These results will help to explain the reported association of the FGFR4-R388 variant with the progression and poor prognosis of certain types of tumors.",
author = "Nami Sugiyama and Markku Varjosalo and Pipsa Meller and Jouko Lohi and Marko Hyyti{\"a}inen and Sami Kilpinen and Olli Kallioniemi and Signe Ingvarsen and Engelholm, {Lars H} and Jussi Taipale and Kari Alitalo and Jorma Keski-Oja and Kaisa Lehti",
note = "{\circledC}2010 AACR.",
year = "2010",
month = "10",
day = "15",
doi = "10.1158/0008-5472.CAN-10-1223",
language = "English",
volume = "70",
pages = "7851--61",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research (A A C R)",
number = "20",

}

RIS

TY - JOUR

T1 - Fibroblast growth factor receptor 4 regulates tumor invasion by coupling fibroblast growth factor signaling to extracellular matrix degradation

AU - Sugiyama, Nami

AU - Varjosalo, Markku

AU - Meller, Pipsa

AU - Lohi, Jouko

AU - Hyytiäinen, Marko

AU - Kilpinen, Sami

AU - Kallioniemi, Olli

AU - Ingvarsen, Signe

AU - Engelholm, Lars H

AU - Taipale, Jussi

AU - Alitalo, Kari

AU - Keski-Oja, Jorma

AU - Lehti, Kaisa

N1 - ©2010 AACR.

PY - 2010/10/15

Y1 - 2010/10/15

N2 - Aberrant expression and polymorphism of fibroblast growth factor receptor 4 (FGFR4) has been linked to tumor progression and anticancer drug resistance. We describe here a novel mechanism of tumor progression by matrix degradation involving epithelial-to-mesenchymal transition in response to membrane-type 1 matrix metalloproteinase (MT1-MMP, MMP-14) induction at the edge of tumors expressing the FGFR4-R388 risk variant. Both FGFR4 and MT1-MMP were upregulated in tissue biopsies from several human cancer types including breast adenocarcinomas, where they were partially coexpressed at the tumor/stroma border and tumor invasion front. The strongest overall coexpression was found in prostate carcinoma. Studies with cultured prostate carcinoma cell lines showed that the FGFR4-R388 variant, which has previously been associated with poor cancer prognosis, increased MT1-MMP-dependent collagen invasion. In this experimental model, knockdown of FGFR4-R388 or MT1-MMP by RNA interference blocked tumor cell invasion and growth in collagen. This was coupled with impaired phosphorylation of FGFR substrate 2 and Src, upregulation of E-cadherin, and suppression of cadherin-11 and N-cadherin. These in vitro results were substantiated by reduced MT1-MMP content and in vivo growth of prostate carcinoma cells after the FGFR4-R388 gene silencing. In contrast, knockdown of the alternative FGFR4-G388 allele enhanced MT1-MMP and invasive tumor cell growth in vivo and within three-dimensional collagen. These results will help to explain the reported association of the FGFR4-R388 variant with the progression and poor prognosis of certain types of tumors.

AB - Aberrant expression and polymorphism of fibroblast growth factor receptor 4 (FGFR4) has been linked to tumor progression and anticancer drug resistance. We describe here a novel mechanism of tumor progression by matrix degradation involving epithelial-to-mesenchymal transition in response to membrane-type 1 matrix metalloproteinase (MT1-MMP, MMP-14) induction at the edge of tumors expressing the FGFR4-R388 risk variant. Both FGFR4 and MT1-MMP were upregulated in tissue biopsies from several human cancer types including breast adenocarcinomas, where they were partially coexpressed at the tumor/stroma border and tumor invasion front. The strongest overall coexpression was found in prostate carcinoma. Studies with cultured prostate carcinoma cell lines showed that the FGFR4-R388 variant, which has previously been associated with poor cancer prognosis, increased MT1-MMP-dependent collagen invasion. In this experimental model, knockdown of FGFR4-R388 or MT1-MMP by RNA interference blocked tumor cell invasion and growth in collagen. This was coupled with impaired phosphorylation of FGFR substrate 2 and Src, upregulation of E-cadherin, and suppression of cadherin-11 and N-cadherin. These in vitro results were substantiated by reduced MT1-MMP content and in vivo growth of prostate carcinoma cells after the FGFR4-R388 gene silencing. In contrast, knockdown of the alternative FGFR4-G388 allele enhanced MT1-MMP and invasive tumor cell growth in vivo and within three-dimensional collagen. These results will help to explain the reported association of the FGFR4-R388 variant with the progression and poor prognosis of certain types of tumors.

U2 - 10.1158/0008-5472.CAN-10-1223

DO - 10.1158/0008-5472.CAN-10-1223

M3 - Journal article

VL - 70

SP - 7851

EP - 7861

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 20

ER -

ID: 32222994