ArticleOncogene2007
The major 8p22 tumor suppressor DLC1 is frequently silenced by methylation in both endemic and sporadic nasopharyngeal, esophageal, and cervical carcinomas, and inhibits tumor cell colony formation.
Article in Oncogene, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 2 of them syntheses that pooled it.
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Who cites it
73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 144 citations in OpenAlex.
- Utility of methylation markers in cervical cancer early detection: appraisal of the state-of-the-science.Gynecologic oncology · 2009Pooled it
- Genomic imbalances in 5918 malignant epithelial tumors: an explorative meta-analysis of chromosomal CGH data.BMC cancer · 2007Pooled it
- Aberrant DNA Methylation in Esophageal Squamous Cell Carcinoma and its Clinical Implications in Systemic Chemotherapy.International journal of medical sciences · 2025Review
- The role of RAC1 in resistance to targeted therapies in cancer.Small GTPases · 2024Review
- ARHGAP6 inhibits bladder cancer cell viability, migration, and invasion via β-catenin signaling and enhances mitomycin C sensitivity.Human cell · 2023Article
- LINC00114 stimulates growth and glycolysis of esophageal cancer cells by recruiting EZH2 to enhance H3K27me3 of DLC1.Clinical epigenetics · 2022Article
- Review
- CpG methylation signature defines human temporal lobe epilepsy and predicts drug-resistant.CNS neuroscience & therapeutics · 2020Article
- Dysregulation of Rho GTPases in Human Cancers.Cancers · 2020Review
- Predictions of the dysregulated competing endogenous RNA signature involved in the progression of human lung adenocarcinoma.Cancer biomarkers : section A of Disease markers · 2020Article
- The phosphoinositide hydrolase phospholipase C delta1 inhibits epithelial-mesenchymal transition and is silenced in colorectal cancer.Journal of cellular physiology · 2019Article
- Epstein-Barr Virus-Induced Epigenetic Pathogenesis of Viral-Associated Lymphoepithelioma-Like Carcinomas and Natural Killer/T-Cell Lymphomas.Pathogens (Basel, Switzerland) · 2018Review
- Article
- Curcumin inhibits growth of human breast cancer cells through demethylation of DLC1 promoter.Molecular and cellular biochemistry · 2017Article
- DNA Oncogenic Virus-Induced Oxidative Stress, Genomic Damage, and Aberrant Epigenetic Alterations.Oxidative medicine and cellular longevity · 2017Review
- Identification of DLC-1 expression and methylation status in patients with non-small-cell lung cancer.Molecular and clinical oncology · 2016Article
- Epigenetic impact of infection on carcinogenesis: mechanisms and applications.Genome medicine · 2016Review
- Low expression of DLC1 is predictive of poor therapeutic efficiency of fluoropyrimidine and oxaliplatin as adjuvant chemotherapy in gastric cancer.Molecular medicine reports · 2015Article
- An Optimization-Driven Analysis Pipeline to Uncover Biomarkers and Signaling Paths: Cervix Cancer.Microarrays (Basel, Switzerland) · 2015Article
- Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 5 countries.
Funding
Abstract
Identification of tumor suppressor genes (TSG) silenced by methylation uncovers mechanisms of tumorigenesis and identifies new epigenetic tumor markers for early cancer detection. Both nasopharyngeal carcinoma (NPC) and esophageal carcinoma are major tumors in Southern China and Southeast Asia. Through expression subtraction of NPC, we identified Deleted in Liver Cancer 1 (DLC1)/ARHGAP7 (NM_006094)--an 8p22 TSG as a major downregulated gene. Although expressed in all normal tissues, DLC1 was silenced or downregulated in 11/12 (91%) NPC, 6/15 (40%) esophageal, 5/8 (63%) cervical and 3/9 (33%) breast carcinoma cell lines. No genetic deletion of DLC1 was detected in NPC although a hemizygous deletion at 8p22-11 was found by 1-Mb array-CGH in some cell lines. We then located the functional DLC1 promoter by 5'-RACE and promoter activity assays. This promoter was frequently methylated in all downregulated cell lines and in a large collection of primary tumors including 89% (64/72) NPC (endemic and sporadic types), 51% (48/94) esophageal, 87% (7/8) cervical and 36% (5/14) breast carcinomas, but seldom in paired surgical marginal tissues and not in any normal epithelial tissue. The transcriptional silencing of DLC1 could be reversed by 5-aza-2'-deoxycytidine or genetic double knock-out of DNMT1 and DNMT3B. Furthermore, ectopic expression of DLC1 in NPC and esophageal carcinoma cells strongly inhibited their colony formation. We thus found frequent epigenetic silencing of DLC1 in NPC, esophageal and cervical carcinomas, and a high correlation of methylation with its downregulation, suggesting a predominant role of epigenetic inactivation. DLC1 appears to be a major TSG implicated in the pathogenesis of these tumors, and should be further tested as a molecular biomarker in patients with these cancers.
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