Tuberin-deficiency downregulates N-cadherin and upregulates vimentin in kidney tumor of TSC patients

Sitai Liang, Tiffanie Salas, Emre Gencaslan, Baojie Li, Samy L. Habib

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Angiomyolipomas (AMLs) are associated with cell fibrosis in kidney of Tuberous Sclerosis Complex patients. The mechanism by which the fibrotic proteins accumulated in AMLs has not been explored. In the present study, we investigated the role of Akt/tuberin/mTOR pathway in the regulation cell fibrosis proteins. AML cells that expressed low levels of tuberin showed less expression of N-cadherin and higher of vimentin proteins compared to HEK293 cells. AML cells infected with Ad-tuberin showed a significant decrease in vimentin and an increase in N-cadherin protein expression. In addition, cells treated with rapamycin showed a significant increase in p-Akt and a decrease in p-p70S6K that was associated with a decrease expression of vimentin and a slight increase expression in N-cadherin. On the other hand, cells treated with Akt inhibitor revealed a significant decrease in p-Akt and p-p70S6K that was associated with a significant decrease in vimentin and an increase in N-cadherin expression. In addition, cells transfected with DN-Akt or DN-S6K show significant increase expression in N-cadherin and a decrease in vimentin. Moreover, cells transfected with siRNA against rictor or siRNA against raptor resulted in a decrease in vimentin and an increase N-cadherin expression. Kidney tumors from TSC patients showed significant decrease in N-cadherin and significant increased in vimentin protein expression compared to control kidney tissues. These data comprise the first report to provide the role of Akt/tuberin/mTORC1/2 in the regulation of N-cadherin and vimentin that are involved in the progression of fibrosis in kidney tumor of TSC patients.

Original languageEnglish (US)
Pages (from-to)6936-6946
Number of pages11
JournalOncotarget
Volume5
Issue number16
DOIs
StatePublished - Jan 1 2014

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Keywords

  • Akt
  • N-cadherin
  • Tuberin
  • Vimentin
  • mTOR and angiomyolipomas

ASJC Scopus subject areas

  • Oncology

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