title: Tuberin-deficiency downregulates N-cadherin and upregulates vimentin in kidney tumor of TSC patients.
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.
authors.affiliation: South Texas Veterans Health Care System, San Antonio, TX.
authors.forename: Sitai
authors.initials: S
authors.lastname: Liang
authors.affiliation: South Texas Veterans Health Care System, San Antonio, TX.
authors.forename: Tiffanie
authors.initials: T
authors.lastname: Salas
authors.affiliation: Akdeniz University Medical School, Antalya, Turkey.
authors.forename: Emre
authors.initials: E
authors.lastname: Gencaslan
authors.affiliation: Bio-X institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Baojie
authors.initials: B
authors.lastname: Li
authors.affiliation: South Texas Veterans Health Care System, San Antonio, TX. Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio and, San Antonio, TX.
authors.forename: Samy L
authors.initials: SL
authors.lastname: Habib
mesh_terms: D018207:Angiomyolipoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D057809:HEK293 Cells; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014402:Tuberous Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000172:deficiency* / Q000378:metabolism; D015854:Up-Regulation; D014746:Vimentin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D014746:Vimentin; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus