FBI1/Akirin2 promotes tumorigenicity and metastasis of Lewis lung carcinoma cells

Biochem Biophys Res Commun. 2014 Feb 14;444(3):382-6. doi: 10.1016/j.bbrc.2014.01.064. Epub 2014 Jan 24.

Abstract

The 14-3-3 family of proteins regulates various signaling pathways involved in cell cycle, apoptosis, stress response, and malignant transformation. We previously demonstrated that the β isoform of the 14-3-3 protein promotes cell growth and tumorigenicity of rat K2 hepatocellular carcinoma cells. We identified fourteen-three-three beta interactant 1 (FBI1)/Akirin2 as a binding partner of 14-3-3β and showed that the complex of these proteins promotes tumorigenicity and metastasis of K2 cells. In addition, we demonstrated that FBI1/Akirin2 downregulation shortened the duration of MAPK activity. Because 14-3-3β and FBI1/Akirin2 overexpression is observed in various cancer cell lines, 14-3-3β-FBI1/Akirin2 oncogenic function should be elucidated in different types of cancer. In this study, we used LLC1 Lewis lung carcinoma cells as a model. We established FBI1/Akirin2 knockdown cell clones through transfection of an antisense FBI1/Akirin2 expression vector and assessed the capacity for cell growth in vitro and tumorigenicity and metastasis in vivo. FBI1/Akirin2 downregulation decreased anchorage-independent growth, whereas the growth rate in monolayer culture was not affected. Moreover, an in vivo assay in nude mice showed that FBI1/Akirin2 overexpression is required for LLC1 tumor growth and metastasis. These results suggest that FBI1/Akirin2 plays an important role in oncogenesis of LLC1 lung carcinoma cells, and this protein may also serve as an oncogene in other cancers.

Keywords: 14-3-3 beta interactant 1/Akirin2; 14-3-3β; Anchorage-independent growth; Metastasis; Tumorigenicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / physiology*
  • Animals
  • Carcinoma, Lewis Lung / pathology*
  • Cell Line, Tumor
  • Neoplasm Metastasis*
  • Rats

Substances

  • 14-3-3 Proteins