| 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 and 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, vol. 111, No 3, p. 1114-1119. ISSN 0027-8424. Available from: https://dx.doi.org/10.1073/pnas.1319551111. |
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@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 = {http://dx.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 and 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, vol.~111, No~3, p.~1114-1119. ISSN~0027-8424. Available from: https://dx.doi.org/10.1073/pnas.1319551111.
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