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

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 fibrosi...

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Published in:	Oncotarget Vol. 5; no. 16; pp. 6936 - 6946
Main Authors:	Liang, Sitai, Salas, Tiffanie, Gencaslan, Emre, Li, Baojie, Habib, Samy L
Format:	Journal Article
Language:	English
Published:	United States Impact Journals LLC 30-08-2014
Subjects:	Angiomyolipoma - genetics Angiomyolipoma - metabolism Angiomyolipoma - pathology Antigens, CD - biosynthesis Antigens, CD - genetics Antigens, CD - metabolism Cadherins - biosynthesis Cadherins - genetics Cadherins - metabolism Down-Regulation HEK293 Cells Humans Kidney Neoplasms - genetics Kidney Neoplasms - metabolism Kidney Neoplasms - pathology Proto-Oncogene Proteins c-akt - antagonists & inhibitors Proto-Oncogene Proteins c-akt - metabolism Research Paper Ribosomal Protein S6 Kinases - metabolism Sirolimus - pharmacology TOR Serine-Threonine Kinases - metabolism Tuberous Sclerosis - genetics Tuberous Sclerosis - metabolism Tuberous Sclerosis - pathology Tumor Suppressor Proteins - deficiency Tumor Suppressor Proteins - metabolism Up-Regulation Vimentin - biosynthesis Vimentin - genetics Vimentin - metabolism
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1949-2553 1949-2553
DOI:	10.18632/oncotarget.2206