title: SIRT1 controls cell proliferation by regulating contact inhibition.
abstract: Contact inhibition keeps cell proliferation in check and serves as a built-in protection against cancer development by arresting cell division upon cell-cell contact. Yet the complete mechanism behind this anti-cancer process remains largely unclear. Here we present SIRT1 as a novel regulator of contact inhibition. SIRT1 performs a wide variety of functions in biological processes, but its involvement in contact inhibition has not been explored to date. We used NIH3T3 cells, which are sensitive to contact inhibition, and H460 and DU145 cancer cells, which lack contact inhibition, to investigate the relationship between SIRT1 and contact inhibition. We show that SIRT1 overexpression in NIH3T3 cells overcomes contact inhibition while SIRT1 knockdown in cancer cells restores their lost contact inhibition. Moreover, we demonstrate that p27 protein expression is controlled by SIRT1 in contact inhibition. Overall, our findings underline the critical role of SIRT1 in contact inhibition and suggest SIRT1 inhibition as a potential strategy to suppress cancer cell growth by restoring contact inhibition.
authors: Cancer Center, Hematology Oncology Section, Department of Medicine, Boston University School of Medicine, 72 East Concord Street, L913, Boston, MA 02118, United States.
authors: Elizabeth H
authors: EH
authors: Cho
authors: Cancer Center, Hematology Oncology Section, Department of Medicine, Boston University School of Medicine, 72 East Concord Street, L913, Boston, MA 02118, United States. Electronic address: yandai@bu.edu.
authors: Yan
authors: Y
authors: Dai
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000235:genetics*; D002455:Cell Division; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D003260:Contact Inhibition / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D019076:Transgenes
chemical_list: C436291:CDKN1B protein, human; D034741:RNA, Small Interfering; D050760:Cyclin-Dependent Kinase Inhibitor p27; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Cell proliferation; Contact inhibition; Malignant transformation; SIRT1; p27