Ect2-Dependent rRNA Synthesis Is Required for KRAS-TRP53-Driven Lung Adenocarcinoma

Verline Justilien, Syed A. Ali, Lee Jamieson, Ning Yin, Adrienne D. Cox, Channing J. Der, Nicole R. Murray, Alan P. Fields

Research output: Contribution to journalArticle

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Abstract

The guanine nucleotide exchange factor (GEF) epithelial cell transforming sequence 2 (Ect2) has been implicated in cancer. However, it is not clear how Ect2 causes transformation and whether Ect2 is necessary for tumorigenesis in vivo. Here, we demonstrate that nuclear Ect2 GEF activity is required for Kras-Trp53 lung tumorigenesis in vivo and that Ect2-mediated transformation requires Ect2-dependent rDNA transcription. Ect2 activates rRNA synthesis by binding the nucleolar transcription factor upstream binding factor 1 (UBF1) on rDNA promoters and recruiting Rac1 and its downstream effector nucleophosmin (NPM) to rDNA. Protein kinase Cι (PKCι)-mediated Ect2 phosphorylation stimulates Ect2-dependent rDNA transcription. Thus, Ect2 regulates rRNA synthesis through a PKCι-Ect2-Rac1-NPM signaling axis that is required for lung tumorigenesis.

LanguageEnglish (US)
Pages256-269
Number of pages14
JournalCancer Cell
Volume31
Issue number2
DOIs
StatePublished - Feb 13 2017

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Epithelial Cells
Ribosomal DNA
Guanine Nucleotide Exchange Factors
Carcinogenesis
EphA2 Receptor
Adenocarcinoma of lung
Lung
Protein Kinases
Phosphorylation
Neoplasms

Keywords

  • Ect2
  • nucleophosmin, NPM
  • protein kinase Cι, PKCι
  • rRNA synthesis
  • tumor initiation
  • upstream binding factor 1, UBF1

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Justilien, V., Ali, S. A., Jamieson, L., Yin, N., Cox, A. D., Der, C. J., ... Fields, A. P. (2017). Ect2-Dependent rRNA Synthesis Is Required for KRAS-TRP53-Driven Lung Adenocarcinoma. Cancer Cell, 31(2), 256-269. DOI: 10.1016/j.ccell.2016.12.010

Ect2-Dependent rRNA Synthesis Is Required for KRAS-TRP53-Driven Lung Adenocarcinoma. / Justilien, Verline; Ali, Syed A.; Jamieson, Lee; Yin, Ning; Cox, Adrienne D.; Der, Channing J.; Murray, Nicole R.; Fields, Alan P.

In: Cancer Cell, Vol. 31, No. 2, 13.02.2017, p. 256-269.

Research output: Contribution to journalArticle

Justilien, V, Ali, SA, Jamieson, L, Yin, N, Cox, AD, Der, CJ, Murray, NR & Fields, AP 2017, 'Ect2-Dependent rRNA Synthesis Is Required for KRAS-TRP53-Driven Lung Adenocarcinoma' Cancer Cell, vol. 31, no. 2, pp. 256-269. DOI: 10.1016/j.ccell.2016.12.010
Justilien V, Ali SA, Jamieson L, Yin N, Cox AD, Der CJ et al. Ect2-Dependent rRNA Synthesis Is Required for KRAS-TRP53-Driven Lung Adenocarcinoma. Cancer Cell. 2017 Feb 13;31(2):256-269. Available from, DOI: 10.1016/j.ccell.2016.12.010
Justilien, Verline ; Ali, Syed A. ; Jamieson, Lee ; Yin, Ning ; Cox, Adrienne D. ; Der, Channing J. ; Murray, Nicole R. ; Fields, Alan P./ Ect2-Dependent rRNA Synthesis Is Required for KRAS-TRP53-Driven Lung Adenocarcinoma. In: Cancer Cell. 2017 ; Vol. 31, No. 2. pp. 256-269
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