Fibroblast Growth Factor Receptor 3 Interacts with and
Activates TGFbeta-Activated Kinase 1 Tyrosine Phosphorylation
and NFkappaB Signaling in Multiple Myeloma and Bladder Cancer

J 2014

Fibroblast Growth Factor Receptor 3 Interacts with and Activates TGFbeta-Activated Kinase 1 Tyrosine Phosphorylation and NFkappaB Signaling in Multiple Myeloma and Bladder Cancer

SALAZAR, Lisa; Tamar KASHIWADA; Pavel KREJČÍ; April MEYER; Malcolm CASALE et. al.

Basic information

Original name

Fibroblast Growth Factor Receptor 3 Interacts with and Activates TGFbeta-Activated Kinase 1 Tyrosine Phosphorylation and NFkappaB Signaling in Multiple Myeloma and Bladder Cancer

Authors

SALAZAR, Lisa (840 United States of America); Tamar KASHIWADA (840 United States of America); Pavel KREJČÍ (203 Czech Republic, guarantor, belonging to the institution); April MEYER (840 United States of America); Malcolm CASALE (840 United States of America); Matthew HALLOWELL (840 United States of America); William WILCOX (840 United States of America); Daniel DONOGHUE (840 United States of America) and Leslie MICHELS THOMPSON (840 United States of America)

Edition

PLOS One, San Francisco, Public Library of Science, 2014, 1932-6203

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30105 Physiology

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 3.234

RIV identification code

RIV/00216224:14310/14:00075111

Organization unit

Faculty of Science

DOI

https://doi.org/10.1371/journal.pone.0086470

UT WoS

000330288000101

EID Scopus

2-s2.0-84899814361

Keywords in English

FGFR3; TAK1; NFkappaB; multiple myeloma; bladder cancer

Abstract

In the original language

Cancer is a major public health problem worldwide. In the United States alone, 1 in 4 deaths is due to cancer and for 2013 a total of 1,660,290 new cancer cases and 580,350 cancer-related deaths are projected. Comprehensive profiling of multiple cancer genomes has revealed a highly complex genetic landscape in which a large number of altered genes, varying from tumor to tumor, impact core biological pathways and processes. This has implications for therapeutic targeting of signaling networks in the development of treatments for specific cancers. The NFkappaB transcription factor is constitutively active in a number of hematologic and solid tumors, and many signaling pathways implicated in cancer are likely connected to NFkappaB activation. A critical mediator of NFkappaB activity is TGFbeta-activated kinase 1 (TAK1). Here, we identify TAK1 as a novel interacting protein and target of fibroblast growth factor receptor 3 (FGFR3) tyrosine kinase activity. We further demonstrate that activating mutations in FGFR3 associated with both multiple myeloma and bladder cancer can modulate expression of genes that regulate NFkappaB signaling, and promote both NFkappaB transcriptional activity and cell adhesion in a manner dependent on TAK1 expression in both cancer cell types. Our findings suggest TAK1 as a potential therapeutic target for FGFR3-associated cancers, and other malignancies in which TAK1 contributes to constitutive NFkappaB activation.

Links

GAP305/11/0752, research and development project

Name: Molekulární základy FGFR3 signalingu v kostní dysplázii

Investor: Czech Science Foundation

LH12004, research and development project

Name: FGFR3-specifický adaptérom a jeho role v patologické FGFR3 signalizaci v nemoci (Acronym: AMVIS-FGFR3)

Investor: Ministry of Education, Youth and Sports of the CR

Cite

SALAZAR, Lisa; Tamar KASHIWADA; Pavel KREJČÍ; April MEYER; Malcolm CASALE; Matthew HALLOWELL; William WILCOX; Daniel DONOGHUE and Leslie MICHELS THOMPSON. Fibroblast Growth Factor Receptor 3 Interacts with and Activates TGFbeta-Activated Kinase 1 Tyrosine Phosphorylation and NFkappaB Signaling in Multiple Myeloma and Bladder Cancer. PLOS One. San Francisco: Public Library of Science, 2014, vol. 9, No 1, p. "nestrankovano", 13 pp. ISSN 1932-6203. Available from: https://doi.org/10.1371/journal.pone.0086470.

@article{1168185,
   author = {Salazar, Lisa and Kashiwada, Tamar and Krejčí, Pavel and Meyer, April and Casale, Malcolm and Hallowell, Matthew and Wilcox, William and Donoghue, Daniel and Michels Thompson, Leslie},
   article_location = {San Francisco},
   article_number = {1},
   doi = {https://doi.org/10.1371/journal.pone.0086470},
   keywords = {FGFR3; TAK1; NFkappaB; multiple myeloma; bladder cancer},
   language = {eng},
   issn = {1932-6203},
   journal = {PLOS One},
   title = {Fibroblast Growth Factor Receptor 3 Interacts with and Activates TGFbeta-Activated Kinase 1 Tyrosine Phosphorylation and NFkappaB Signaling in Multiple Myeloma and Bladder Cancer},
   url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900522/},
   volume = {9},
   year = {2014}
}

TY  - JOUR
ID  - 1168185
AU  - Salazar, Lisa - Kashiwada, Tamar - Krejčí, Pavel - Meyer, April - Casale, Malcolm - Hallowell, Matthew - Wilcox, William - Donoghue, Daniel - Michels Thompson, Leslie
PY  - 2014
TI  - Fibroblast Growth Factor Receptor 3 Interacts with and Activates TGFbeta-Activated Kinase 1 Tyrosine Phosphorylation and NFkappaB Signaling in Multiple Myeloma and Bladder Cancer
JF  - PLOS One
VL  - 9
IS  - 1
SP  - "nestrankovano"
EP  - "nestrankovano"
PB  - Public Library of Science
SN  - 19326203
KW  - FGFR3
KW  - TAK1
KW  - NFkappaB
KW  - multiple myeloma
KW  - bladder cancer
UR  - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900522/
L2  - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900522/
N2  - Cancer is a major public health problem worldwide. In the United States alone, 1 in 4 deaths is due to cancer and for 2013 a total of 1,660,290 new cancer cases and 580,350 cancer-related deaths are projected. Comprehensive profiling of multiple cancer genomes has revealed a highly complex genetic landscape in which a large number of altered genes, varying from tumor to tumor, impact core biological pathways and processes. This has implications for therapeutic targeting of signaling networks in the development of treatments for specific cancers. The NFkappaB transcription factor is constitutively active in a number of hematologic and solid tumors, and many signaling pathways implicated in cancer are likely connected to NFkappaB activation. A critical mediator of NFkappaB activity is TGFbeta-activated kinase 1 (TAK1). Here, we identify TAK1 as a novel interacting protein and target of fibroblast growth factor receptor 3 (FGFR3) tyrosine kinase activity. We further demonstrate that activating mutations in FGFR3 associated with both multiple myeloma and bladder cancer can modulate expression of genes that regulate NFkappaB signaling, and promote both NFkappaB transcriptional activity and cell adhesion in a manner dependent on TAK1 expression in both cancer cell types. Our findings suggest TAK1 as a potential therapeutic target for FGFR3-associated cancers, and other malignancies in which TAK1 contributes to constitutive NFkappaB activation.
ER  -

SALAZAR, Lisa; Tamar KASHIWADA; Pavel KREJČÍ; April MEYER; Malcolm CASALE; Matthew HALLOWELL; William WILCOX; Daniel DONOGHUE and Leslie MICHELS THOMPSON. Fibroblast Growth Factor Receptor 3 Interacts with and Activates TGFbeta-Activated Kinase 1 Tyrosine Phosphorylation and NFkappaB Signaling in Multiple Myeloma and Bladder Cancer. \textit{PLOS One}. San Francisco: Public Library of Science, 2014, vol.~9, No~1, p.~''nestrankovano'', 13 pp. ISSN~1932-6203. Available from: https://doi.org/10.1371/journal.pone.0086470.

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