A novel protein tyrosine kinase NOK that shares homology with platelet-derived growth factor/fibroblast growth factor receptors induces tumorigenesis and metastasis in nude mice

Li Liu, Xin Zi Yu, Tie Shi Li, Lian Xia Song, Pei La Chen, Ta Lin Suo, Ying Hua Li, Shi Dong Wang, Yue Chen, Yong Ming Ren, Shu Ping Zhang, Zhi Jie Chang, Xin Yuan Fu

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Receptor protein tyrosine kinases (RPTKs) play important roles in the regulation of a variety of cellular processes including cell migration, proliferation, and protection from apoptosis. Here, we report the identification and characterization of a novel RPTK-like molecule that has a critical role in induction of tumorigenesis and metastasis and is termed Novel Oncogene with Kinase-domain (NOK). NOK contains a putative single transmembrane domain and a conserved intracellular tyrosine kinase domain that shares homology with members of the platelet-derived growth factor/fibroblast growth factor receptor superfamily. NOK was exclusively located in the cytoplasm. NOK mRNAs were detected in limited human organs and expressed with the highest abundance in the prostate. A variety of tumor cells also expressed the NOK mRNAs. We demonstrated that NIH3T3 and BaF3 cells could be strongly transformed by the expression of the NOK gene as examined by colony formation experiment. In addition, BaF3 cells with the stable expression of NOK induced rapid tumorigenesis in nude mice. Interestingly, these NOK-expressing tumor cells could promptly invade and spread into various distinct organs and form metastatic foci, eventually leading to the rapid death of these animals. Moreover, molecular mechanism studies indicated that NOK could concomitantly activate both MAP kinase and phosphatidylinositol 3′-kinases (PI3K) pathways in stable BaF3 cells. Thus, our results both in vitro and in vivo suggest that NOK is a novel oncogene with the capacity of promoting cell transformation, tumorigenesis, and metastasis.

Original languageEnglish (US)
Pages (from-to)3491-3499
Number of pages9
JournalCancer Research
Volume64
Issue number10
DOIs
StatePublished - May 15 2004
Externally publishedYes

Fingerprint

Fibroblast Growth Factor Receptors
Platelet-Derived Growth Factor
Oncogenes
Nude Mice
Protein-Tyrosine Kinases
Carcinogenesis
Phosphotransferases
Neoplasm Metastasis
Receptor Protein-Tyrosine Kinases
Messenger RNA
Cytoprotection
Phosphatidylinositol 3-Kinases
Cell Movement
Prostate
Neoplasms
Cytoplasm
Cell Proliferation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A novel protein tyrosine kinase NOK that shares homology with platelet-derived growth factor/fibroblast growth factor receptors induces tumorigenesis and metastasis in nude mice. / Liu, Li; Yu, Xin Zi; Li, Tie Shi; Song, Lian Xia; Chen, Pei La; Suo, Ta Lin; Li, Ying Hua; Wang, Shi Dong; Chen, Yue; Ren, Yong Ming; Zhang, Shu Ping; Chang, Zhi Jie; Fu, Xin Yuan.

In: Cancer Research, Vol. 64, No. 10, 15.05.2004, p. 3491-3499.

Research output: Contribution to journalArticle

Liu, L, Yu, XZ, Li, TS, Song, LX, Chen, PL, Suo, TL, Li, YH, Wang, SD, Chen, Y, Ren, YM, Zhang, SP, Chang, ZJ & Fu, XY 2004, 'A novel protein tyrosine kinase NOK that shares homology with platelet-derived growth factor/fibroblast growth factor receptors induces tumorigenesis and metastasis in nude mice', Cancer Research, vol. 64, no. 10, pp. 3491-3499. https://doi.org/10.1158/0008-5472.CAN-03-2106
Liu, Li ; Yu, Xin Zi ; Li, Tie Shi ; Song, Lian Xia ; Chen, Pei La ; Suo, Ta Lin ; Li, Ying Hua ; Wang, Shi Dong ; Chen, Yue ; Ren, Yong Ming ; Zhang, Shu Ping ; Chang, Zhi Jie ; Fu, Xin Yuan. / A novel protein tyrosine kinase NOK that shares homology with platelet-derived growth factor/fibroblast growth factor receptors induces tumorigenesis and metastasis in nude mice. In: Cancer Research. 2004 ; Vol. 64, No. 10. pp. 3491-3499.
@article{c5fed84d114445bf880cfb88538411fe,
title = "A novel protein tyrosine kinase NOK that shares homology with platelet-derived growth factor/fibroblast growth factor receptors induces tumorigenesis and metastasis in nude mice",
abstract = "Receptor protein tyrosine kinases (RPTKs) play important roles in the regulation of a variety of cellular processes including cell migration, proliferation, and protection from apoptosis. Here, we report the identification and characterization of a novel RPTK-like molecule that has a critical role in induction of tumorigenesis and metastasis and is termed Novel Oncogene with Kinase-domain (NOK). NOK contains a putative single transmembrane domain and a conserved intracellular tyrosine kinase domain that shares homology with members of the platelet-derived growth factor/fibroblast growth factor receptor superfamily. NOK was exclusively located in the cytoplasm. NOK mRNAs were detected in limited human organs and expressed with the highest abundance in the prostate. A variety of tumor cells also expressed the NOK mRNAs. We demonstrated that NIH3T3 and BaF3 cells could be strongly transformed by the expression of the NOK gene as examined by colony formation experiment. In addition, BaF3 cells with the stable expression of NOK induced rapid tumorigenesis in nude mice. Interestingly, these NOK-expressing tumor cells could promptly invade and spread into various distinct organs and form metastatic foci, eventually leading to the rapid death of these animals. Moreover, molecular mechanism studies indicated that NOK could concomitantly activate both MAP kinase and phosphatidylinositol 3′-kinases (PI3K) pathways in stable BaF3 cells. Thus, our results both in vitro and in vivo suggest that NOK is a novel oncogene with the capacity of promoting cell transformation, tumorigenesis, and metastasis.",
author = "Li Liu and Yu, {Xin Zi} and Li, {Tie Shi} and Song, {Lian Xia} and Chen, {Pei La} and Suo, {Ta Lin} and Li, {Ying Hua} and Wang, {Shi Dong} and Yue Chen and Ren, {Yong Ming} and Zhang, {Shu Ping} and Chang, {Zhi Jie} and Fu, {Xin Yuan}",
year = "2004",
month = "5",
day = "15",
doi = "10.1158/0008-5472.CAN-03-2106",
language = "English (US)",
volume = "64",
pages = "3491--3499",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "10",

}

TY - JOUR

T1 - A novel protein tyrosine kinase NOK that shares homology with platelet-derived growth factor/fibroblast growth factor receptors induces tumorigenesis and metastasis in nude mice

AU - Liu, Li

AU - Yu, Xin Zi

AU - Li, Tie Shi

AU - Song, Lian Xia

AU - Chen, Pei La

AU - Suo, Ta Lin

AU - Li, Ying Hua

AU - Wang, Shi Dong

AU - Chen, Yue

AU - Ren, Yong Ming

AU - Zhang, Shu Ping

AU - Chang, Zhi Jie

AU - Fu, Xin Yuan

PY - 2004/5/15

Y1 - 2004/5/15

N2 - Receptor protein tyrosine kinases (RPTKs) play important roles in the regulation of a variety of cellular processes including cell migration, proliferation, and protection from apoptosis. Here, we report the identification and characterization of a novel RPTK-like molecule that has a critical role in induction of tumorigenesis and metastasis and is termed Novel Oncogene with Kinase-domain (NOK). NOK contains a putative single transmembrane domain and a conserved intracellular tyrosine kinase domain that shares homology with members of the platelet-derived growth factor/fibroblast growth factor receptor superfamily. NOK was exclusively located in the cytoplasm. NOK mRNAs were detected in limited human organs and expressed with the highest abundance in the prostate. A variety of tumor cells also expressed the NOK mRNAs. We demonstrated that NIH3T3 and BaF3 cells could be strongly transformed by the expression of the NOK gene as examined by colony formation experiment. In addition, BaF3 cells with the stable expression of NOK induced rapid tumorigenesis in nude mice. Interestingly, these NOK-expressing tumor cells could promptly invade and spread into various distinct organs and form metastatic foci, eventually leading to the rapid death of these animals. Moreover, molecular mechanism studies indicated that NOK could concomitantly activate both MAP kinase and phosphatidylinositol 3′-kinases (PI3K) pathways in stable BaF3 cells. Thus, our results both in vitro and in vivo suggest that NOK is a novel oncogene with the capacity of promoting cell transformation, tumorigenesis, and metastasis.

AB - Receptor protein tyrosine kinases (RPTKs) play important roles in the regulation of a variety of cellular processes including cell migration, proliferation, and protection from apoptosis. Here, we report the identification and characterization of a novel RPTK-like molecule that has a critical role in induction of tumorigenesis and metastasis and is termed Novel Oncogene with Kinase-domain (NOK). NOK contains a putative single transmembrane domain and a conserved intracellular tyrosine kinase domain that shares homology with members of the platelet-derived growth factor/fibroblast growth factor receptor superfamily. NOK was exclusively located in the cytoplasm. NOK mRNAs were detected in limited human organs and expressed with the highest abundance in the prostate. A variety of tumor cells also expressed the NOK mRNAs. We demonstrated that NIH3T3 and BaF3 cells could be strongly transformed by the expression of the NOK gene as examined by colony formation experiment. In addition, BaF3 cells with the stable expression of NOK induced rapid tumorigenesis in nude mice. Interestingly, these NOK-expressing tumor cells could promptly invade and spread into various distinct organs and form metastatic foci, eventually leading to the rapid death of these animals. Moreover, molecular mechanism studies indicated that NOK could concomitantly activate both MAP kinase and phosphatidylinositol 3′-kinases (PI3K) pathways in stable BaF3 cells. Thus, our results both in vitro and in vivo suggest that NOK is a novel oncogene with the capacity of promoting cell transformation, tumorigenesis, and metastasis.

UR - http://www.scopus.com/inward/record.url?scp=2442690630&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2442690630&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-03-2106

DO - 10.1158/0008-5472.CAN-03-2106

M3 - Article

C2 - 15150103

AN - SCOPUS:2442690630

VL - 64

SP - 3491

EP - 3499

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 10

ER -