| First Author | Kalakonda S | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 45 | Pages | E4213-22 |
| PubMed ID | 24145455 | Mgi Jnum | J:202910 |
| Mgi Id | MGI:5523366 | Doi | 10.1073/pnas.1303760110 |
| Citation | Kalakonda S, et al. (2013) Monoallelic loss of tumor suppressor GRIM-19 promotes tumorigenesis in mice. Proc Natl Acad Sci U S A 110(45):E4213-22 |
| abstractText | Gene-associated with retinoid-interferon induced mortality-19 (GRIM-19), a STAT3-inhibitory protein, was isolated as a growth-suppressive gene product using a genome-wide expression knockdown screen. We and others have shown a loss of expression and occurrence of mutations in the GRIM-19 gene in a variety of primary human cancers, indicating its potential role as tumor suppressor. To help investigate its role in tumor development in vivo, we generated a genetically modified mouse in which Grim-19 can be conditionally inactivated. Deletion of Grim-19 in the skin significantly increased the susceptibility of mice to chemical carcinogenesis, resulting in development of squamous cell carcinomas. These tumors had high Stat3 activity and an increased expression of Stat3-responsive genes. Loss of Grim-19 also caused mitochondrial electron transport dysfunction resulting from failure to assemble electron transport chain complexes and altered the expression of several cellular genes involved in glycolysis. Surprisingly, the deletion of a single copy of the Grim-19 gene was sufficient to promote carcinogenesis and formation of invasive squamous cell carcinomas. These observations highlight the critical role of GRIM-19 as a tumor suppressor. |
