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Updated: Aug 29, 2026
An Efficient Method for Directed Hepatocyte-Like Cell Induction from Human Embryonic Stem Cells
Published on: May 6, 2021
Isolation of development and differentiation enhancing factor-like 1 (DDEFL1) as a drug target for hepatocellular
Hiroshi Okabe1, Yoichi Furukawa, Tatsushi Kato
1Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Abstract:
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.
Insights
Researchers identified a novel gene, DDEFL1, crucial for hepatocellular carcinoma (HCC) development. This discovery offers potential new diagnostic markers and therapeutic targets for liver cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Hepatocellular carcinoma (HCC) is a major global health concern with complex carcinogenic mechanisms.
- Identifying novel molecular targets is crucial for improving HCC diagnosis and treatment strategies.
Purpose of the Study:
- To elucidate the mechanisms underlying hepatocellular carcinogenesis.
- To discover novel diagnostic markers and potential therapeutic targets for HCC.
Main Methods:
- Genome-wide cDNA microarray analysis of clinical HCC samples.
- Identification and characterization of a novel gene, DDEFL1.
- Functional studies involving gene transfer and antisense oligonucleotide inhibition.
Main Results:
- A novel human gene, DDEFL1, was identified and found to be commonly up-regulated in HCC tumors.
- DDEFL1 encodes a protein with structural similarities to centaurin-family proteins, including an ArfGAP domain.
- Overexpression of DDEFL1 promoted cell proliferation, while its inhibition suppressed cancer cell growth.
Conclusions:
- DDEFL1 plays a significant role in promoting HCC cell proliferation and may be involved in hepatocarcinogenesis.
- The findings provide novel insights into liver cancer mechanisms.
- DDEFL1 represents a potential diagnostic marker and therapeutic target for HCC.
