Direct in vivo RNAi screen unveils myosin IIa as a tumor suppressor of squamous cell carcinomas.

Abstract

Mining modern genomics for cancer therapies is predicated on weeding out "bystander" alterations (nonconsequential mutations) and identifying "driver" mutations responsible for tumorigenesis and/or metastasis. We used a direct in vivo RNA interference (RNAi) strategy to screen for genes that upon repression predispose mice to squamous cell carcinomas (SCCs). Seven of our top hits-including Myh9, which encodes nonmuscle myosin IIa-have not been linked to tumor development, yet tissue-specific Myh9 RNAi and Myh9 knockout trigger invasive SCC formation on tumor-susceptible backgrounds. In human and mouse keratinocytes, myosin IIa's function is manifested not only in conventional actin-related processes but also in regulating posttranscriptional p53 stabilization. Myosin IIa is diminished in human SCCs with poor survival, which suggests that in vivo RNAi technology might be useful for identifying potent but low-penetrance tumor suppressors.

• Authors: Daniel Schramek, Ataman Sendoel, Jeremy P Segal, Slobodan Beronja, Evan Heller, Daniel Oristian, Boris Reva, Elaine Fuchs
• Journal: Science (New York, N.Y.) (Science) Vol. 343 Issue 6168 Pg. 309-13 (Jan 17 2014) ISSN: 1095-9203 [Electronic] United States
• PMID: 24436421 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• MYH9 protein, human
• Molecular Motor Proteins
• Myh9 protein, mouse
• Tumor Suppressor Protein p53
• Tumor Suppressor Proteins
• Nonmuscle Myosin Type IIA
• Myosin Heavy Chains

Topics

• Animals
• Carcinoma, Squamous Cell (genetics, pathology)
• Genetic Testing
• Head and Neck Neoplasms (genetics, pathology)
• Humans
• Lung Neoplasms (secondary)
• Mice
• Mice, Knockout
• Molecular Motor Proteins (genetics, physiology)
• Mutation
• Myosin Heavy Chains (genetics, physiology)
• Nonmuscle Myosin Type IIA (genetics, physiology)
• RNA Interference
• Transcription, Genetic
• Tumor Suppressor Protein p53 (genetics)
• Tumor Suppressor Proteins (genetics, physiology)