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High-throughput Screening and Biosensing with Fluorescent C. elegans Strains
Published on: May 19, 2011
An approach using Caenorhabditis elegans screening novel targets to suppress tumour cell proliferation
Yu-Qin Mao1,2, San-Feng Han1,2, Shi-Long Zhang1,2
1Key Laboratory of Whole-period Monitoring and Precise Intervention of Digestive Cancer (SMHC), Minhang Hospital, Fudan University, Shanghai, China.
Objectives:
Tumour cell proliferation requires high metabolism to meet the bioenergetics and biosynthetic needs. Dauer in Caenorhabditis elegans is characterized by lower metabolism, and we established an approach with C elegans to find potential tumour therapy targets.
Materials And Methods:
RNAi screening was used to find dauer-related genes, and these genes were further analysed in glp-1(-) mutants for tumour-suppressing testing. The identified tumour-related genes were verified in clinical tumour tissues.
Results:
The lifespan of glp-1(-) mutants was found to be extended by classical dauer formation signalling. Then, 61 of 287 kinase-coding genes in Caenorhabditis elegans were identified as dauer-related genes, of which 27 were found to be homologous to human oncogenes. Furthermore, 12 dauer-related genes were randomly selected for tumour-suppressing test, and six genes significantly extended the lifespan of glp-1(-) mutants. Of these six genes, F47D12.9, W02B12.12 and gcy-21 were newly linked to dauer formation. These three new dauer-related genes significantly suppressed tumour cell proliferation and thus extended the lifespan of glp-1(-) mutants in a longevity- or dauer-independent manner. The mRNA expression profiles indicated that these dauer-related genes trigged similar low metabolism pattern in glp-1(-) mutants. Notably, the expression of homolog gene DCAF4L2/F47D12.9, TSSK6/W02B12.12 and NPR1/gcy-21 was found to be higher in glioma compared with adjacent normal tissue. In addition, the high expression of TSSK6/W02B12.12 and NPR1/gcy-21 correlated with a worse survival in glioma patients.
Conclusions:
Dauer gene screening in combination with tumour-suppressing test in glp-1(-) mutants provided a useful approach to find potential targets for tumour therapy via suppressing tumour cell proliferation and rewiring tumour cell metabolism.
Insights
This study used Caenorhabditis elegans to identify genes involved in dauer formation that could suppress tumour growth. Three novel genes were found to reduce tumour cell proliferation and lower metabolism, offering potential cancer therapy targets.
Area of Science:
- Genetics and Molecular Biology
- Developmental Biology
- Cancer Research
Background:
- Tumour cell proliferation necessitates high metabolism for energy and biosynthesis.
- The dauer state in Caenorhabditis elegans is associated with reduced metabolism.
- Identifying targets that can lower cancer cell metabolism is crucial for therapy.
Purpose of the Study:
- To establish a C. elegans model for identifying potential tumour therapy targets by studying dauer formation.
- To screen for genes involved in dauer formation that exhibit tumour-suppressing properties.
- To investigate the metabolic rewiring effects of identified genes on tumour cells.
Main Methods:
- RNA interference (RNAi) screening was employed to identify dauer-related genes in C. elegans.
- Identified genes were tested for tumour-suppressing activity in glp-1(-) mutants.
- The expression of homologous genes was analyzed in clinical tumour tissues (glioma).
Main Results:
- Sixty-one dauer-related kinase-coding genes were identified, with 27 homologous to human oncogenes.
- Six of twelve tested dauer-related genes significantly extended the lifespan of glp-1(-) mutants.
- Three novel dauer-related genes (F47D12.9, W02B12.12, gcy-21) suppressed tumour cell proliferation independently of longevity or dauer pathways, inducing a low metabolism pattern.
- Higher expression of homologous genes (DCAF4L2, TSSK6, NPR1) was observed in glioma tissues, with TSSK6 and NPR1 correlating with poorer patient survival.
Conclusions:
- Dauer gene screening in C. elegans provides a viable strategy for discovering tumour therapy targets.
- Targeting dauer-related genes can suppress tumour cell proliferation and alter cancer cell metabolism.
- Novel genes like F47D12.9, W02B12.12, and gcy-21 represent promising candidates for cancer treatment development.
