STANDARD_NAME	ODONNELL_TARGETS_OF_MYC_AND_TFRC_DN
SYSTEMATIC_NAME	M6792
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/ODONNELL_TARGETS_OF_MYC_AND_TFRC_DN
NAMESPACE	AFFY_HG_U133
DESCRIPTION_BRIEF	Genes up-regulated in P493-6 cells (B lymphocyte, Burkitt's lymphoma model) by MYC [GeneID=4609] and down-regulated by RNAi knockdown of TFRC [GeneID=7037].
DESCRIPTION_FULL	Overexpression of transferrin receptor 1 (TFRC1), a major mediator of iron uptake in mammalian cells, is a common feature of human malignancies. Therapeutic strategies designed to interfere with tumor iron metabolism have targeted TFRC1. The c-Myc oncogenic transcription factor stimulates proliferation and growth by activating thousands of target genes. Here we demonstrate that TFRC1 is a critical downstream target of c-Myc. Using in vitro and in vivo models of B-cell lymphoma, we show that TFRC1 expression is activated by c-Myc. Chromatin immunoprecipitation experiments reveal that c-Myc directly binds a conserved region of TFRC1. In light of these findings, we sought to determine whether TFRC1 is required for c-Myc-mediated cellular proliferation and cell size control. TFRC1 inhibition decreases cellular proliferation and results in G1 arrest without affecting cell size. Consistent with these findings, expression profiling reveals that TFRC1 depletion alters expression of genes that regulate the cell cycle. Furthermore, enforced TFRC1 expression confers a growth advantage to cells and significantly enhances the rate of c-Myc-mediated tumor formation in vivo. These findings provide a molecular basis for increased TFRC1 expression in human tumors, illuminate the role of TFRC1 in the c-Myc target gene network, and support strategies that target TFRC1 for cancer therapy.
PMID	16508012
GEOID	
AUTHORS	O'Donnell KA,Yu D,Zeller KI,Kim JW,Racke F,Thomas-Tikhonenko A,Dang CV
CONTRIBUTOR	Leona Saunders
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 7BS
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	1555413_s_at,1558320_at,1565717_s_at,1566109_at,201291_s_at,201710_at,201897_s_at,202095_s_at,202482_x_at,202580_x_at,202870_s_at,203213_at,203214_x_at,203418_at,203755_at,203968_s_at,203976_s_at,204092_s_at,204244_s_at,204306_s_at,204492_at,205909_at,208079_s_at,209053_s_at,209172_s_at,209464_at,209891_at,210334_x_at,210559_s_at,211088_s_at,211708_s_at,213226_at,213647_at,214358_at,214727_at,217448_s_at,219650_at,222958_s_at,223700_at,224496_s_at,225834_at,226980_at,227350_at,228535_at,228729_at,229349_at,231128_at,232278_s_at,235088_at,235545_at,235573_at,237215_s_at,238506_at,238704_at,239835_at,239973_at,242890_at,244396_at
GENE_SYMBOLS	,,FUS,,TOP2A,MYBL2,CKS1B,BIRC5,RANBP1,FOXM1,CDC20,CDK1,CDK1,CCNA2,BUB1B,CDC6,CHAF1A,AURKA,DBF4,CD151,ARHGAP11A,POLE2,AURKA,NSD2,CENPF,AURKB,SPC25,BIRC5,CDK1,PLK4,SCD,CCNA2,DNA2,ACACA,BRCA2,TOX4,ERCC6L,DEPDC1,MND1,TMEM107,FAM72C,DEPDC1B,HELLS,RAD1,CCNB1,LIN28B,FAM181B,DEPDC1,C4orf46,DEPDC1,HSPH1,TFRC,LRRC58,,KBTBD8,SNHG26,HELLS,G3BP1
FOUNDER_NAMES