Oncogenic Ect2 signaling regulates rRNA synthesis in NSCLC

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The Rho GTPase family members Rac1, Cdc42 and RhoA play key contributory roles in the transformed phenotype of human cancers. Epithelial Cell Transforming Sequence 2 (Ect2), a guanine nucleotide exchange factor (GEF) for these Rho GTPases, has also been implicated in a variety of human cancers. We have shown that Ect2 is frequently overexpressed in both major forms of non-small cell lung cancer (NSCLC), lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC), which together make up approximately 70% of all lung cancer diagnoses. Furthermore, we have found that Ect2 is required for multiple aspects of the transformed phenotype of NSCLC cells including transformed growth and invasion in vitro and tumorigenesis in vivo. More recently, we showed that a major mechanism by which Ect2 drives KRAS-mediated LADC transformation is by regulating rRNA (rRNA) synthesis. However, it remains unclear whether Ect2 plays a similar role in ribosome biogenesis in LSCC. Here we demonstrate that Ect2 expression correlates positively with expression of ribosome biogenesis genes and with pre-ribosomal 45S RNA abundance in primary LSCC tumors. Furthermore, we demonstrate that Ect2 functionally regulates rRNA synthesis in LSCC cells. Based on these data, we propose that inhibition of Ect2-mediated nucleolar signaling holds promise as a potential therapeutic strategy for improved treatment of both LADC and LSCC.

Original languageEnglish (US)
Pages (from-to)388-394
Number of pages7
JournalSmall GTPases
Volume10
Issue number5
DOIs
StatePublished - Sep 3 2019

Keywords

  • Ect2
  • non-small cell lung cancer
  • ribosome biogenesis
  • rRNA synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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