title: Novel c-MYC target genes mediate differential effects on cell proliferation and migration.
abstract: The developmental and oncogenic roles of MYC proteins are well established, but the transcriptional targets mediating their functions remain elusive. Using small interfering RNA-mediated knockdown in breast and cervix carcinoma cell lines, which overexpress c-MYC, we show that c-MYC independently controls metabolism and cell proliferation, and can, depending on the cells, promote or inhibit migration. We identified new c-MYC target genes in these cell lines, and show that selective regulation of some targets correlates with the phenotypic responses of these different cell lines to c-MYC depletion. Notably, we show that a positive regulation of the WNT signalling pathway contributes to c-MYC pro-mitogenic effects in breast and cervix carcinoma cells. We also show that repression of CCL5/RANTES accounts for c-MYC anti-migratory effects in specific breast cancer cells. Our combined genomic and phenotypic analysis indicates that c-MYC functions are cellular-context-dependent and that selectively regulated genes are responsible for its differential properties.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland. cappellen@igr.fr
authors.forename: David
authors.initials: D
authors.lastname: Cappellen
authors.forename: Thomas
authors.initials: T
authors.lastname: Schlange
authors.forename: Matthieu
authors.initials: M
authors.lastname: Bauer
authors.forename: Francisca
authors.initials: F
authors.lastname: Maurer
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Hynes
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D018946:Chemokine CCL5 / Q000235:genetics; D019742:Chemokines, CC / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics
chemical_list: C483024:CCL5 protein, human; D018946:Chemokine CCL5; D019742:Chemokines, CC; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D051153:Wnt Proteins