Publication Date:
2014-01-18
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159249/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159249/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schramek, Daniel -- Sendoel, Ataman -- Segal, Jeremy P -- Beronja, Slobodan -- Heller, Evan -- Oristian, Daniel -- Reva, Boris -- Fuchs, Elaine -- R37 AR027883/AR/NIAMS NIH HHS/ -- R37-AR27883/AR/NIAMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Jan 17;343(6168):309-13. doi: 10.1126/science.1248627.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436421" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Carcinoma, Squamous Cell/*genetics/*pathology
;
Genetic Testing
;
Head and Neck Neoplasms/genetics/pathology
;
Humans
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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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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