Journal article
Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
Journal of Visualized Experiments, Vol.2020(164), pp.1-10
10/05/2020
DOI: 10.3791/61788
PMID: 33074252
Abstract
The changes in the plasma membrane localization of the epidermal growth factor receptor (EGFR) and its downstream effector RAS have been implicated in several diseases including cancer. The free-living nematode C. elegans possesses an evolutionary and functionally conserved EGFR-RAS-ERK MAP signal cascade which is central for the development of the vulva. Gain of function mutations in RAS homolog LET-60 and EGFR homolog LET-23 induce the generation of visible nonfunctional ectopic pseudovulva along the ventral body wall of these worms. Previously, the multivulval (Muv) phenotype in these worms has been shown to be inhibited by small chemical molecules. Here we describe a protocol for using the worm in a liquid-based assay to identify inhibitors that abolish the activities of EGFR and RAS proteins. Using this assay, we show R-fendiline, an indirect inhibitor of K-RAS, suppresses the Muv phenotype expressed in the let-60(n1046) and let-23(sa62) mutant worms. The assay is simple, inexpensive, is not time consuming to setup, and can be used as an initial platform for the discovery of anticancer therapeutics.
Details
- Title: Subtitle
- Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
- Creators
- Dharini van der Hoeven - The University of Texas Health Science Center at HoustonThuy Nhu L. Truong - Department of Diagnostic and Biomedical Sciences, School of Dentistry, University of Texas Health Science CenterAli Naji - Department of Diagnostic and Biomedical Sciences, School of Dentistry, University of Texas Health Science CenterSabita Thapa - Department of Diagnostic and Biomedical Sciences, School of Dentistry, University of Texas Health Science CenterJohn F. Hancock - The University of Texas Health Science Center at HoustonRansome van der Hoeven - Department of Diagnostic and Biomedical Sciences, School of Dentistry, University of Texas Health Science Center
- Resource Type
- Journal article
- Publication Details
- Journal of Visualized Experiments, Vol.2020(164), pp.1-10
- Publisher
- MyJove Corporation
- DOI
- 10.3791/61788
- PMID
- 33074252
- ISSN
- 1940-087X
- eISSN
- 1940-087X
- Language
- English
- Date published
- 10/05/2020
- Academic Unit
- Oral Pathology, Radiology and Medicine; Dentistry Administration; Dental Research; Periodontics
- Record Identifier
- 9984738105302771
Metrics
3 Record Views