Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To disclose mechanisms of hepatocellular carcinogenesis and to identify novel diagnostic markers and/or drug targets for treatment of hepatocellular carcinomas (HCCs), we analyzed expression profiles of clinical HCCs using a genome-wide cDNA microarray. From among the transcripts that were commonly up-regulated in these tumors we identified a novel human gene at chromosomal band 1p36.13, termed DDEFL1 (development and differentiation enhancing factor-like 1), encoding a product that shared structural features with centaurin-family proteins. The deduced 903-amino acid sequence showed 46% homology to DDEF/ASAP1 (development and differentiation enhancing factor), and contained an Arf GTPase-activating protein (ArfGAP) domain and two ankyrin repeats. Gene transfer of DDEFL1 promoted proliferation of cells that lacked endogenous expression of this gene. Furthermore, reduction of DDEFL1 expression by transfection of anti-sense S-oligonucleotides inhibited the growth of SNU475 cancer cells, in which DDEFL1 expression was highly up-regulated. Our results provide novel insight into hepatocarcinogenesis and may contribute to development of new strategies for diagnosis and treatment of HCC.
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PMID:Isolation of development and differentiation enhancing factor-like 1 (DDEFL1) as a drug target for hepatocellular carcinomas. 1465 39

ASAP3, an Arf GTPase-activating protein previously called DDEFL1 and ACAP4, has been implicated in the pathogenesis of hepatocellular carcinoma. We have examined in vitro and in vivo functions of ASAP3 and compared it to the related Arf GAP ASAP1 that has also been implicated in oncogenesis. ASAP3 was biochemically similar to ASAP1: the pleckstrin homology domain affected function of the catalytic domain by more than 100-fold; catalysis was stimulated by phosphatidylinositol 4,5-bisphosphate; and Arf1, Arf5, and Arf6 were used as substrates in vitro. Like ASAP1, ASAP3 associated with focal adhesions and circular dorsal ruffles. Different than ASAP1, ASAP3 did not localize to invadopodia or podosomes. Cells, derived from a mammary carcinoma and from a glioblastoma, with reduced ASAP3 expression had fewer actin stress fiber, reduced levels of phosphomyosin, and migrated more slowly than control cells. Reducing ASAP3 expression also slowed invasion of mammary carcinoma cells. In contrast, reduction of ASAP1 expression had no effect on migration or invasion. We propose that ASAP3 functions nonredundantly with ASAP1 to control cell movement and may have a role in cancer cell invasion. In comparing ASAP1 and ASAP3, we also found that invadopodia are dispensable for the invasive behavior of cells derived from a mammary carcinoma.
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PMID:ASAP3 is a focal adhesion-associated Arf GAP that functions in cell migration and invasion. 1840 Jul 62