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

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

105 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",

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

language = "English",

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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.

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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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