Vimentin is a novel AKT1 target mediating motility and invasion

Q. S. Zhu, K. Rosenblatt, Kai-Lieh Huang, G. Lahat, R. Brobey, S. Bolshakov, T. Nguyen, Z. Ding, R. Belousov, K. Bill, X. Luo, A. Lazar, A. Dicker, G. B. Mills, M. C. Hung, D. Lev

Research output: Contribution to journalArticle

106 Scopus citations

Abstract

The PI3K/AKT signaling pathway is aberrant in a wide variety of cancers. Downstream effectors of AKT are involved in survival, growth and metabolic-related pathways. In contrast, contradictory data relating to AKT effects on cell motility and invasion, crucial prometastatic processes, have been reported pointing to a potential cell type and isoform type-specific AKT-driven function. By implication, study of AKT signaling should optimally be conducted in an appropriate intracellular environment. Prognosis in soft-tissue sarcoma (STS), the aggressive malignancies of mesenchymal origin, is poor, reflecting our modest ability to control metastasis, an effort hampered by lack of insight into molecular mechanisms driving STS progression and dissemination. We examined the impact of the cancer progression-relevant AKT pathway on the mesenchymal tumor cell internal milieu. We demonstrate that AKT1 activation induces STS cell motility and invasiveness at least partially through a novel interaction with the intermediate filament vimentin (Vim). The binding of AKT (tail region) to Vim (head region) results in Vim Ser39 phosphorylation enhancing the ability of Vim to induce motility and invasion while protecting Vim from caspase-induced proteolysis. Moreover, vimentin phosphorylation was shown to enhance tumor and metastasis growth in vivo. Insights into this mesenchymal-related molecular mechanism may facilitate the development of critically lacking therapeutic options for these devastating malignancies.

Original languageEnglish (US)
Pages (from-to)457-470
Number of pages14
JournalOncogene
Volume30
Issue number4
DOIs
StatePublished - Jan 27 2011
Externally publishedYes

    Fingerprint

Keywords

  • AKT1
  • migration/invasion
  • phosphorylation
  • soft-tissue sarcoma
  • vimentin

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Zhu, Q. S., Rosenblatt, K., Huang, K-L., Lahat, G., Brobey, R., Bolshakov, S., Nguyen, T., Ding, Z., Belousov, R., Bill, K., Luo, X., Lazar, A., Dicker, A., Mills, G. B., Hung, M. C., & Lev, D. (2011). Vimentin is a novel AKT1 target mediating motility and invasion. Oncogene, 30(4), 457-470. https://doi.org/10.1038/onc.2010.421