How do K-RAS-activated cells evade cellular defense mechanisms?
Lung adenocarcinomas, like other cancers, develop through the accumulation of epigenetic and genetic alterations. Numerous studies have shown that K-RAS mutation is among the most important early events in carcinogenesis of the lung. However, it is also well established that growth-stimulating signa...
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Nature Publishing Group
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761642/ |
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pubmed-47616422016-03-04 How do K-RAS-activated cells evade cellular defense mechanisms? Lee, Y-S Bae, S-C Review Lung adenocarcinomas, like other cancers, develop through the accumulation of epigenetic and genetic alterations. Numerous studies have shown that K-RAS mutation is among the most important early events in carcinogenesis of the lung. However, it is also well established that growth-stimulating signals feed back into growth-suppressing pathways, and any imbalance in these signaling networks will cause the cell to exit the cell cycle, thereby preventing uncontrolled cell growth. How, then, do K-RAS-activated cells evade cellular defense mechanisms? To answer this question, it is necessary to identify the molecular event(s) responsible for the development of early dysplastic lesions that are unable to defend against aberrant oncogene activation. Lineage-determining transcriptional regulators govern differentiation status during normal lung development, as well as in lung adenocarcinoma. Among the genes involved in K-RAS-induced lung tumorigenesis, RUNX3 is unique: inactivation of Runx3 in mouse lung induces lung adenoma and abrogates the ARF–p53 pathway. This observation raises the possibility of intimate cross-talk between the differentiation program and oncogene surveillance. In this review, we summarized evidences suggesting that K-RAS-activated cells do not evade cellular defense mechanisms per se; instead, cells with K-RAS mutations are selected only if they occur in cells in which defense mechanism is abrogated. Nature Publishing Group 2016-02-18 2015-05-11 /pmc/articles/PMC4761642/ /pubmed/25961920 http://dx.doi.org/10.1038/onc.2015.153 Text en Copyright © 2016 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Lee, Y-S Bae, S-C |
| spellingShingle |
Lee, Y-S Bae, S-C How do K-RAS-activated cells evade cellular defense mechanisms? |
| author_facet |
Lee, Y-S Bae, S-C |
| author_sort |
Lee, Y-S |
| title |
How do K-RAS-activated cells evade cellular defense mechanisms? |
| title_short |
How do K-RAS-activated cells evade cellular defense mechanisms? |
| title_full |
How do K-RAS-activated cells evade cellular defense mechanisms? |
| title_fullStr |
How do K-RAS-activated cells evade cellular defense mechanisms? |
| title_full_unstemmed |
How do K-RAS-activated cells evade cellular defense mechanisms? |
| title_sort |
how do k-ras-activated cells evade cellular defense mechanisms? |
| description |
Lung adenocarcinomas, like other cancers, develop through the accumulation of epigenetic and genetic alterations. Numerous studies have shown that K-RAS mutation is among the most important early events in carcinogenesis of the lung. However, it is also well established that growth-stimulating signals feed back into growth-suppressing pathways, and any imbalance in these signaling networks will cause the cell to exit the cell cycle, thereby preventing uncontrolled cell growth. How, then, do K-RAS-activated cells evade cellular defense mechanisms? To answer this question, it is necessary to identify the molecular event(s) responsible for the development of early dysplastic lesions that are unable to defend against aberrant oncogene activation. Lineage-determining transcriptional regulators govern differentiation status during normal lung development, as well as in lung adenocarcinoma. Among the genes involved in K-RAS-induced lung tumorigenesis, RUNX3 is unique: inactivation of Runx3 in mouse lung induces lung adenoma and abrogates the ARF–p53 pathway. This observation raises the possibility of intimate cross-talk between the differentiation program and oncogene surveillance. In this review, we summarized evidences suggesting that K-RAS-activated cells do not evade cellular defense mechanisms per se; instead, cells with K-RAS mutations are selected only if they occur in cells in which defense mechanism is abrogated. |
| publisher |
Nature Publishing Group |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761642/ |
| _version_ |
1613541316817321984 |