STANDARD_NAME	TAGHAVI_NEOPLASTIC_TRANSFORMATION
SYSTEMATIC_NAME	M9267
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/TAGHAVI_NEOPLASTIC_TRANSFORMATION
NAMESPACE	Human_RefSeq
DESCRIPTION_BRIEF	Genes that cooperate with MYC and TBX2 [GeneID=4609;6909] to transform MEF cells (embryo fibroblasts).
DESCRIPTION_FULL	c-Myc drives uncontrolled cell proliferation in various human cancers. However, in mouse embryo fibroblasts (MEFs), c-Myc also induces apoptosis by activating the p19Arf tumor suppressor pathway. Tbx2, a transcriptional repressor of p19Arf, can collaborate with c-Myc by suppressing apoptosis. MEFs overexpressing c-Myc and Tbx2 are immortal but not transformed. We have performed an unbiased genetic screen, which identified 12 oncogenes that collaborate with c-Myc and Tbx2 to transform MEFs in vitro. One of them encodes the LPA2 receptor for the lipid growth factor lysophosphatidic acid (LPA). We find that LPA1 and LPA4, but not LPA3, can reproduce the transforming effect of LPA2. Using pharmacological inhibitors, we show that the in vitro cell transformation induced by LPA receptors is dependent on the Gi-linked ERK and PI3K signaling pathways. The transforming ability of LPA1, LPA2 and LPA4 was confirmed by tumor formation assays in vivo and correlated with prolonged ERK1/2 activation in response to LPA. Our results reveal a direct role for LPA receptor signaling in cell transformation and tumorigenesis in conjunction with c-Myc and reduced p19Arf expression.
PMID	18762810
GEOID	
AUTHORS	Taghavi P,Verhoeven E,Jacobs JJ,Lambooij JP,Stortelers C,Tanger E,Moolenaar WH,van Lohuizen M
CONTRIBUTOR	Jessica Robertson
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 1
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	NM_001458,NM_002608,NM_002880,NM_004712,NM_004924,NM_006732,NM_014397,NM_014552,NM_020028,NM_024979,NM_198576,NM_203351
GENE_SYMBOLS	FLNC,PDGFB,RAF1,HGS,ACTN4,FOSB,NEK6,,LPAR2,MCF2L,AGRN,MAP3K3
FOUNDER_NAMES