C. elegans as a model organism for in vivo screening in cancer: effects of human c-Met in lung cancer affect C. elegans vulva phenotypes

Cancer Biol Ther. 2008 Jun;7(6):856-63. doi: 10.4161/cbt.7.6.5842. Epub 2008 Mar 5.


Cancers typically harbour several mutant forms of key cellular genes that contribute to its complex phenotype. Our lab has previously identified gain-of-function mutations in some of the receptor tyrosine kinases such as c-Met in lung cancer. In order to investigate the mutant gene in the context of a whole organism, the current choice of in vivo model is limited to the mouse. To rapidly screen the functional aspects of mutant forms of c-Met detected in lung cancer, we used the nematode C. elegans as the model organism. Transgenic worms were generated that harbour wild type or the frequently seen mutant forms of c-Met in lung cancer (c-MetR988C and c-MetT1010I). Expression of the mutant human c-Met forms in C. elegans consistently resulted in significantly low fecundity and abnormal vulval development characterized by hyperplasia. Interestingly, exposure of c-Met mutant transgenic worms to nicotine resulted in enhanced abnormal vulval development, fecundity and locomotion. Our studies provide first evidence that human c-Met mutations can be studied in C. elegans, and that carcinogens can enhance mutant c-Met function expressed in C. elegans transgenic animals. We therefore propose the use of C. elegans as a model to rapidly assess the role of cancer specific gene mutations in the context of a whole organism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Antineoplastic Agents / pharmacology*
  • Caenorhabditis elegans
  • Drug Screening Assays, Antitumor*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology*
  • Mutation
  • Nicotine / chemistry
  • Phenotype
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-met / biosynthesis*
  • Proto-Oncogene Proteins c-met / genetics*
  • RNA Interference
  • Vulva / drug effects*
  • Vulva / pathology*


  • Antineoplastic Agents
  • Nicotine
  • Proto-Oncogene Proteins c-met