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Review
. 2010:2010:150960.
doi: 10.1155/2010/150960. Epub 2010 Jun 7.

Clinical relevance of KRAS in human cancers

Sylwia Jancík  1 , Jirí Drábek, Danuta Radzioch, Marián Hajdúch
Affiliations
Review

Clinical relevance of KRAS in human cancers

Sylwia Jancík et al. J Biomed Biotechnol. 2010.

Abstract

The KRAS gene (Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) is an oncogene that encodes a small GTPase transductor protein called KRAS. KRAS is involved in the regulation of cell division as a result of its ability to relay external signals to the cell nucleus. Activating mutations in the KRAS gene impair the ability of the KRAS protein to switch between active and inactive states, leading to cell transformation and increased resistance to chemotherapy and biological therapies targeting epidermal growth factor receptors. This review highlights some of the features of the KRAS gene and the KRAS protein and summarizes current knowledge of the mechanism of KRAS gene regulation. It also underlines the importance of activating mutations in the KRAS gene in relation to carcinogenesis and their importance as diagnostic biomarkers, providing clues regarding human cancer patients' prognosis and indicating potential therapeutic approaches.

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Figures

Figure 1
Figure 1
Signaling pathway of the KRAS protein. Following EGF binding to its receptor and activation of tyrosine kinases, the KRAS protein becomes activated by binding to GTP, transducing the activation signal to the nucleus by MAPKs and PI3K/AKT-mediated cascades. Specifically, the active state of the KRAS protein is facilitated by binding to the Grb2 protein, which interacts with the SH3 domains of the SOS protein, a member of the nucleotide exchange factor family. In the GTP state, KRAS is able to activate downstream proteins and to regulate cell transformation.
Figure 2
Figure 2
Activity states of the KRAS protein. Mutational change in exon 1 of KRAS leads to permanent “on” status.
Figure 3
Figure 3
Model of the KRAS protein with important domains highlighted. Model of 3GFT molecule was rendered in Swiss-PdbViewer v4.0.1 (http://spdbv.vital-it.ch/). Switch 1, Switch 2, and GTP P-loop domains are highlighted by colour change.
Figure 4
Figure 4
Position of codon 12 in KRAS molecule. Wild type aminoacid at codon 12 is shown in green.
See this image and copyright information in PMC

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