In:
Molecular Cancer Research, American Association for Cancer Research (AACR), Vol. 11, No. 9 ( 2013-09-01), p. 1072-1077
Abstract:
Activating point mutations in K-RAS are extremely common in cancers of the lung, colon, and pancreas and are highly predictive of poor therapeutic response. One potential strategy for overcoming the deleterious effects of mutant K-RAS is to alter its posttranslational modification. Although therapies targeting farnesylation have been explored, and have ultimately failed, the therapeutic potential of targeting other modifications remains to be seen. Recently, it was shown that acetylation of lysine 104 attenuates K-RAS transforming activity by interfering with GEF-induced nucleotide exchange. Here, the deacetylases HDAC6 and SIRT2 were shown to regulate the acetylation state of K-RAS in cancer cells. By extension, inhibition of either of these enzymes has a dramatic impact on the growth properties of cancer cells expressing activation mutants of K-RAS. These results suggest that therapeutic targeting of HDAC6 and/or SIRT2 may represent a new way to treat cancers expressing mutant forms of K-RAS. Implications: This study suggests that altering K-RAS acetylation is a feasible approach to limiting tumorigenic potential. Mol Cancer Res; 11(9); 1072–7. ©2013 AACR.
Type of Medium:
Online Resource
ISSN:
1541-7786
,
1557-3125
DOI:
10.1158/1541-7786.MCR-13-0040-T
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2013
detail.hit.zdb_id:
2097884-4
SSG:
12
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