title: The inhibition of Nek6 function sensitizes human cancer cells to premature senescence upon serum reduction or anticancer drug treatment.
abstract: The induction of premature senescence in cancer cells was proposed as an effective cancer treatment strategy. In this paper, we show that the inhibition of Nek6 expression by Nek6 siRNA-mediated knockdown or the overexpression of a dominant negative form of Nek6 (Nek6KM) induced premature senescence as well as cell death under reduced serum conditions in multiple cancer cell lines, including both p53 wild-type and p53 mutant/null backgrounds. Moreover, cancer cells expressing Nek6KM exhibited significantly increased premature senescence upon treatment with the anticancer drugs doxorubicin (DOX) and camptothecin (CPT). Significantly, the overexpression of Nek6KM also inhibited tumor growth and promoted premature senescence in vivo in a xenograft mouse model. Taken together, our results further confirm that Nek6 plays an important role in the premature senescence of cancer cells, suggesting that Nek6 may be a potential therapeutic target for human cancers.
authors: Department of Biochemistry, College of Medicine, Dong-A University, Busan 602-714, South Korea.
authors: Hye Jin
authors: HJ
authors: Jee
authors: Hyun-Ju
authors: HJ
authors: Kim
authors: Ae Jeong
authors: AJ
authors: Kim
authors: Naree
authors: N
authors: Song
authors: Minjee
authors: M
authors: Kim
authors: Hye-Jeong
authors: HJ
authors: Lee
authors: Jeanho
authors: J
authors: Yun
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D016203:CDC2 Protein Kinase; D002166:Camptothecin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects*; D016895:Culture Media, Serum-Free; D019926:Cyclin B / Q000378:metabolism; D018844:Cyclin-Dependent Kinases; D004317:Doxorubicin / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005799:Genes, Dominant; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D000072379:NIMA-Related Kinases; D009368:Neoplasm Transplantation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D016895:Culture Media, Serum-Free; D019926:Cyclin B; D050505:Mutant Proteins; D017382:Reactive Oxygen Species; D004317:Doxorubicin; C459456:NEK6 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D002166:Camptothecin