Runx3 Inactivation Is a Crucial Early Event in the Development of Lung Adenocarcinoma

You Soub Lee; Jung Won Lee; Ju Won Jang; Xin Zi Chi; Jang Hyun Kim; Ying Hui Li; Min Kyu Kim; Da Mi Kim; Byeung Sub Choi; Eung Gook Kim; Jin Haeng Chung; Ok Jun Lee; You Mie Lee; Joo Won Suh; Linda Shyue Huey Chuang; Yoshiaki Ito; Suk Chul Bae

doi:10.1016/j.ccr.2013.10.003

Runx3 Inactivation Is a Crucial Early Event in the Development of Lung Adenocarcinoma

You Soub Lee
, Jung Won Lee
, Ju Won Jang
, Xin Zi Chi
, Jang Hyun Kim
, Ying Hui Li
, Min Kyu Kim
, Da Mi Kim
, Byeung Sub Choi
, Eung Gook Kim
, Jin Haeng Chung
, Ok Jun Lee
, You Mie Lee
, Joo Won Suh
, Linda Shyue Huey Chuang
, Yoshiaki Ito
, Suk Chul Bae

Chungbuk National University
Seoul National University
Myongji University
National University of Singapore

Research output: Contribution to journal › Article › peer-review

110 Scopus citations

Abstract

Targeted inactivation of Runx3 in mouse lung induced mucinous and nonmucinous adenomas and markedly shortened latency of adenocarcinoma formation induced by oncogenic K-Ras. RUNX3 was frequently inactivated in K-RAS mutated human lung adenocarcinomas. A functional genetic screen of a fly mutant library and molecular analysis in cultured cell lines revealed that Runx3 forms a complex with BRD2 in a K-Ras-dependent manner in the early phase of the cell cycle; this complex induces expression of p14^ARF/p19^Arf and p21^WAF/CIP. When K-Ras was constitutively activated, the Runx3-BRD2 complex was stably maintained and expression of both p14^ARF and p21^WAF/CIP was prolonged. These results provide a missing link between oncogenic K-Ras and the p14^ARF-p53 pathway, and may explain how cells defend against oncogenic K-Ras.

Original language	English
Pages (from-to)	603-616
Number of pages	14
Journal	Cancer Cell
Volume	24
Issue number	5
DOIs	https://doi.org/10.1016/j.ccr.2013.10.003
State	Published - 11 Nov 2013

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Lee, Y. S., Lee, J. W., Jang, J. W., Chi, X. Z., Kim, J. H., Li, Y. H., Kim, M. K., Kim, D. M., Choi, B. S., Kim, E. G., Chung, J. H., Lee, O. J., Lee, Y. M., Suh, J. W., Chuang, L. S. H., Ito, Y., & Bae, S. C. (2013). Runx3 Inactivation Is a Crucial Early Event in the Development of Lung Adenocarcinoma. Cancer Cell, 24(5), 603-616. https://doi.org/10.1016/j.ccr.2013.10.003

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title = "Runx3 Inactivation Is a Crucial Early Event in the Development of Lung Adenocarcinoma",

abstract = "Targeted inactivation of Runx3 in mouse lung induced mucinous and nonmucinous adenomas and markedly shortened latency of adenocarcinoma formation induced by oncogenic K-Ras. RUNX3 was frequently inactivated in K-RAS mutated human lung adenocarcinomas. A functional genetic screen of a fly mutant library and molecular analysis in cultured cell lines revealed that Runx3 forms a complex with BRD2 in a K-Ras-dependent manner in the early phase of the cell cycle; this complex induces expression of p14ARF/p19Arf and p21WAF/CIP. When K-Ras was constitutively activated, the Runx3-BRD2 complex was stably maintained and expression of both p14ARF and p21WAF/CIP was prolonged. These results provide a missing link between oncogenic K-Ras and the p14ARF-p53 pathway, and may explain how cells defend against oncogenic K-Ras.",

author = "Lee, \{You Soub\} and Lee, \{Jung Won\} and Jang, \{Ju Won\} and Chi, \{Xin Zi\} and Kim, \{Jang Hyun\} and Li, \{Ying Hui\} and Kim, \{Min Kyu\} and Kim, \{Da Mi\} and Choi, \{Byeung Sub\} and Kim, \{Eung Gook\} and Chung, \{Jin Haeng\} and Lee, \{Ok Jun\} and Lee, \{You Mie\} and Suh, \{Joo Won\} and Chuang, \{Linda Shyue Huey\} and Yoshiaki Ito and Bae, \{Suk Chul\}",

year = "2013",

month = nov,

day = "11",

doi = "10.1016/j.ccr.2013.10.003",

language = "English",

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journal = "Cancer Cell",

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T1 - Runx3 Inactivation Is a Crucial Early Event in the Development of Lung Adenocarcinoma

AU - Lee, You Soub

AU - Lee, Jung Won

AU - Jang, Ju Won

AU - Chi, Xin Zi

AU - Kim, Jang Hyun

AU - Li, Ying Hui

AU - Kim, Min Kyu

AU - Kim, Da Mi

AU - Choi, Byeung Sub

AU - Kim, Eung Gook

AU - Chung, Jin Haeng

AU - Lee, Ok Jun

AU - Lee, You Mie

AU - Suh, Joo Won

AU - Chuang, Linda Shyue Huey

AU - Ito, Yoshiaki

AU - Bae, Suk Chul

PY - 2013/11/11

Y1 - 2013/11/11

N2 - Targeted inactivation of Runx3 in mouse lung induced mucinous and nonmucinous adenomas and markedly shortened latency of adenocarcinoma formation induced by oncogenic K-Ras. RUNX3 was frequently inactivated in K-RAS mutated human lung adenocarcinomas. A functional genetic screen of a fly mutant library and molecular analysis in cultured cell lines revealed that Runx3 forms a complex with BRD2 in a K-Ras-dependent manner in the early phase of the cell cycle; this complex induces expression of p14ARF/p19Arf and p21WAF/CIP. When K-Ras was constitutively activated, the Runx3-BRD2 complex was stably maintained and expression of both p14ARF and p21WAF/CIP was prolonged. These results provide a missing link between oncogenic K-Ras and the p14ARF-p53 pathway, and may explain how cells defend against oncogenic K-Ras.

AB - Targeted inactivation of Runx3 in mouse lung induced mucinous and nonmucinous adenomas and markedly shortened latency of adenocarcinoma formation induced by oncogenic K-Ras. RUNX3 was frequently inactivated in K-RAS mutated human lung adenocarcinomas. A functional genetic screen of a fly mutant library and molecular analysis in cultured cell lines revealed that Runx3 forms a complex with BRD2 in a K-Ras-dependent manner in the early phase of the cell cycle; this complex induces expression of p14ARF/p19Arf and p21WAF/CIP. When K-Ras was constitutively activated, the Runx3-BRD2 complex was stably maintained and expression of both p14ARF and p21WAF/CIP was prolonged. These results provide a missing link between oncogenic K-Ras and the p14ARF-p53 pathway, and may explain how cells defend against oncogenic K-Ras.

UR - https://www.scopus.com/pages/publications/84887533067

U2 - 10.1016/j.ccr.2013.10.003

DO - 10.1016/j.ccr.2013.10.003

M3 - Article

C2 - 24229708

AN - SCOPUS:84887533067

SN - 1535-6108

VL - 24

SP - 603

EP - 616

JO - Cancer Cell

JF - Cancer Cell

IS - 5

ER -

Runx3 Inactivation Is a Crucial Early Event in the Development of Lung Adenocarcinoma

Abstract

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