Frequent mutation of receptor protein tyrosine phosphatases
provides a mechanism for STAT3 hyperactivation in head and neck
cancer

J 2014

Frequent mutation of receptor protein tyrosine phosphatases provides a mechanism for STAT3 hyperactivation in head and neck cancer

LUI, Vivian Way Y.; Noah D. PEYSER; Patrick KS NG; Jozef HRITZ; Yan ZENG et. al.

Základní údaje

Originální název

Frequent mutation of receptor protein tyrosine phosphatases provides a mechanism for STAT3 hyperactivation in head and neck cancer

Autoři

Vydání

Proceedings of the National Academy of Sciences of the United States of America, WASHINGTON, NATL ACAD SCIENCES, 2014, 0027-8424

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30000 3. Medical and Health Sciences

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 9.674

Kód RIV

RIV/00216224:14740/14:00075085

Organizační jednotka

Středoevropský technologický institut

DOI

https://doi.org/10.1073/pnas.1319551111

UT WoS

000329928400059

EID Scopus

2-s2.0-84892928970

Klíčová slova anglicky

STAT3 activation; driver mutations; phosphatase mutations

Štítky

kontrola MP, ok, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 17. 10. 2014 12:49, Martina Prášilová

Anotace

V originále

The underpinnings of STAT3 hyperphosphorylation resulting in enhanced signaling and cancer progression are incompletely understood. Loss-of-function mutations of enzymes that dephosphorylate STAT3, such as receptor protein tyrosine phosphatases, which are encoded by the PTPR gene family, represent a plausible mechanism of STAT3 hyperactivation. We analyzed whole exome sequencing (n = 374) and reverse-phase protein array data (n = 212) from head and neck squamous cell carcinomas (HNSCCs). PTPR mutations are most common and are associated with significantly increased phospho-STAT3 expression in HNSCC tumors. Expression of receptor-like protein tyrosine phosphatase T (PTPRT) mutant proteins induces STAT3 phosphorylation and cell survival, consistent with a "driver" phenotype. Computational modeling reveals functional consequences of PTPRT mutations on phospho-tyrosine-substrate interactions. A high mutation rate (30%) of PTPRs was found in HNSCC and 14 other solid tumors, suggesting that PTPR alterations, in particular PTPRT mutations, may define a subset of patients where STAT3 pathway inhibitors hold particular promise as effective therapeutic agents.

Citovat

LUI, Vivian Way Y.; Noah D. PEYSER; Patrick KS NG; Jozef HRITZ; Yan ZENG; Yiling LU; Hua LI; Lins WANG; Breean R. GILBERT; Ignacio J. GENERAL; Ivet BAHAR; Zhenlin JU; Zhenghe WANG; Kelsey P. PENDLETON; Xiao XIAO; Yu DU; John K. VRIES; Peter S. HAMMERMAN; Levi A. GARRAWAY; Gordon B. MILLS; Dean Kim JOHNSON a Jennifer R. GRANDIS. Frequent mutation of receptor protein tyrosine phosphatases provides a mechanism for STAT3 hyperactivation in head and neck cancer. Proceedings of the National Academy of Sciences of the United States of America. WASHINGTON: NATL ACAD SCIENCES, 2014, roč. 111, č. 3, s. 1114-1119. ISSN 0027-8424. Dostupné z: https://doi.org/10.1073/pnas.1319551111.

@article{1166988,
   author = {Lui, Vivian Way Y. and Peyser, Noah D. and Ng, Patrick KS and Hritz, Jozef and Zeng, Yan and Lu, Yiling and Li, Hua and Wang, Lins and Gilbert, Breean R. and General, Ignacio J. and Bahar, Ivet and Ju, Zhenlin and Wang, Zhenghe and Pendleton, Kelsey P. and Xiao, Xiao and Du, Yu and Vries, John K. and Hammerman, Peter S. and Garraway, Levi A. and Mills, Gordon B. and Johnson, Dean Kim and Grandis, Jennifer R.},
   article_location = {WASHINGTON},
   article_number = {3},
   doi = {https://doi.org/10.1073/pnas.1319551111},
   keywords = {STAT3 activation; driver mutations; phosphatase mutations},
   language = {eng},
   issn = {0027-8424},
   journal = {Proceedings of the National Academy of Sciences of the United States of America},
   title = {Frequent mutation of receptor protein tyrosine phosphatases provides a mechanism for STAT3 hyperactivation in head and neck cancer},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/24395800},
   volume = {111},
   year = {2014}
}

TY  - JOUR
ID  - 1166988
AU  - Lui, Vivian Way Y. - Peyser, Noah D. - Ng, Patrick KS - Hritz, Jozef - Zeng, Yan - Lu, Yiling - Li, Hua - Wang, Lins - Gilbert, Breean R. - General, Ignacio J. - Bahar, Ivet - Ju, Zhenlin - Wang, Zhenghe - Pendleton, Kelsey P. - Xiao, Xiao - Du, Yu - Vries, John K. - Hammerman, Peter S. - Garraway, Levi A. - Mills, Gordon B. - Johnson, Dean Kim - Grandis, Jennifer R.
PY  - 2014
TI  - Frequent mutation of receptor protein tyrosine phosphatases provides a mechanism for STAT3 hyperactivation in head and neck cancer
JF  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 111
IS  - 3
SP  - 1114-1119
EP  - 1114-1119
PB  - NATL ACAD SCIENCES
SN  - 00278424
KW  - STAT3 activation
KW  - driver mutations
KW  - phosphatase mutations
UR  - http://www.ncbi.nlm.nih.gov/pubmed/24395800
L2  - http://www.ncbi.nlm.nih.gov/pubmed/24395800
N2  - The underpinnings of STAT3 hyperphosphorylation resulting in enhanced signaling and cancer progression are incompletely understood. Loss-of-function mutations of enzymes that dephosphorylate STAT3, such as receptor protein tyrosine phosphatases, which are encoded by the PTPR gene family, represent a plausible mechanism of STAT3 hyperactivation. We analyzed whole exome sequencing (n = 374) and reverse-phase protein array data (n = 212) from head and neck squamous cell carcinomas (HNSCCs). PTPR mutations are most common and are associated with significantly increased phospho-STAT3 expression in HNSCC tumors. Expression of receptor-like protein tyrosine phosphatase T (PTPRT) mutant proteins induces STAT3 phosphorylation and cell survival, consistent with a "driver" phenotype. Computational modeling reveals functional consequences of PTPRT mutations on phospho-tyrosine-substrate interactions. A high mutation rate (30%) of PTPRs was found in HNSCC and 14 other solid tumors, suggesting that PTPR alterations, in particular PTPRT mutations, may define a subset of patients where STAT3 pathway inhibitors hold particular promise as effective therapeutic agents.
ER  -

LUI, Vivian Way Y.; Noah D. PEYSER; Patrick KS NG; Jozef HRITZ; Yan ZENG; Yiling LU; Hua LI; Lins WANG; Breean R. GILBERT; Ignacio J. GENERAL; Ivet BAHAR; Zhenlin JU; Zhenghe WANG; Kelsey P. PENDLETON; Xiao XIAO; Yu DU; John K. VRIES; Peter S. HAMMERMAN; Levi A. GARRAWAY; Gordon B. MILLS; Dean Kim JOHNSON a Jennifer R. GRANDIS. Frequent mutation of receptor protein tyrosine phosphatases provides a mechanism for STAT3 hyperactivation in head and neck cancer. \textit{Proceedings of the National Academy of Sciences of the United States of America}. WASHINGTON: NATL ACAD SCIENCES, 2014, roč.~111, č.~3, s.~1114-1119. ISSN~0027-8424. Dostupné z: https://doi.org/10.1073/pnas.1319551111.

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