title: Both mTORC1 and mTORC2 are involved in the regulation of cell adhesion.
abstract: mTOR is a central controller for cell growth/proliferation and survival. Recent studies have shown that mTOR also regulates cell adhesion, yet the underlying mechanism is not known. Here we found that inhibition of mTOR by rapamycin reduced the basal or type I insulin-like growth factor (IGF-1)-stimulated adhesion of cancer cells. Further research revealed that both mTORC1 and mTORC2 were involved in the regulation of cell adhesion, as silencing expression of raptor or rictor inhibited cell adhesion. Also, PP242, an mTORC1/2 kinase inhibitor, inhibited cell adhesion more potently than rapamycin (mTORC1 inhibitor). Of interest, ectopic expression of constitutively active and rapamycin-resistant mutant of p70 kinase 1 (S6K1) or downregulation of eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) conferred resistance to rapamycin inhibition of cell adhesion, whereas expression of constitutively hypophosphorylated 4E-BP1 (4EBP1-5A) or downregulation of S6K1 suppressed cell adhesion. In contrast, neither genetic manipulation of Akt activity nor pharmacological inhibition of Akt affected cell adhesion. The results suggest that both mTORC1 and mTORC2 are involved in the regulation of cell adhesion; and mTORC1 regulates cell adhesion through S6K1 and 4E-BP1 pathways, but mTORC2 regulates cell adhesion via Akt-independent mechanism.
authors.affiliation: Jiangsu Key Laboratory for Microbes and Functional Genomics, Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, P. R. China.|Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: Baoshan
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory for Microbes and Functional Genomics, Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, P. R. China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Barzegar
authors.affiliation: Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.|Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Chung
authors.affiliation: Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.|Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: Shile
authors.initials: S
authors.lastname: Huang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D002448:Cell Adhesion; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002470:Cell Survival; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012208:Rhabdomyosarcoma / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D039561:Eukaryotic Initiation Factor-4E; D046912:Multiprotein Complexes; D010750:Phosphoproteins; D007334:Insulin-Like Growth Factor I; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1
keywords: 4E-BP1; Akt; cell adhesion; mTOR; rapamycin