Kirsten Ras* oncogene: Significance of its discovery in human cancer research

Tsuchida, Nobuo; Murugan, Avaniyapuram Kannan; Grieco, Michèle

doi:10.18632/oncotarget.8773

Cited by 66 publications

(41 citation statements)

References 140 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, it has been shown in the clinic that decreases in PDGF and TGFβ levels after radiotherapy for breast cancer can cause echocardiographic alterations affecting cardiovascular morbidity [86]. We also observed the highest frequency of the KRAS pathway, a known oncogene [87], being impacted as a function dose ( Figure 7A). It has been previously described in experiments with single ion species that KRAS can induce lung cancer due to HZE particles [14].…”

Section: Discussionsupporting

confidence: 55%

NASA GeneLab Platform Utilized for Biological Response to Space Radiation in Animal Models

McDonald¹,

Stainforth

Cahill

et al. 2020

Cancers

View full text Add to dashboard Cite

Background: Ionizing radiation from galactic cosmic rays (GCR) is one of the major risk factors that will impact the health of astronauts on extended missions outside the protective effects of the Earth’s magnetic field. The NASA GeneLab project has detailed information on radiation exposure using animal models with curated dosimetry information for spaceflight experiments. Methods: We analyzed multiple GeneLab omics datasets associated with both ground-based and spaceflight radiation studies that included in vivo and in vitro approaches. A range of ions from protons to iron particles with doses from 0.1 to 1.0 Gy for ground studies, as well as samples flown in low Earth orbit (LEO) with total doses of 1.0 mGy to 30 mGy, were utilized. Results: From this analysis, we were able to identify distinct biological signatures associating specific ions with specific biological responses due to radiation exposure in space. For example, we discovered changes in mitochondrial function, ribosomal assembly, and immune pathways as a function of dose. Conclusions: We provided a summary of how the GeneLab’s rich database of omics experiments with animal models can be used to generate novel hypotheses to better understand human health risks from GCR exposures.

show abstract

Section: Discussionsupporting

confidence: 55%

NASA GeneLab Platform Utilized for Biological Response to Space Radiation in Animal Models

McDonald¹,

Stainforth

Cahill

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…However, this by itself is not sufficient to drive the development of PDA, and additional external signaling is needed to raise oncogenic KRas activity to levels where it drives an inflammatory program that leads to a feed-forward loop [9,10]. Sustained activation of signaling pathways downstream of mutant KRas then drive cancer cell survival, proliferation, migration and invasion [11]. Inactivating mutations in the tumor suppressor genes CDKN2A , TP53 and SMAD4 also promote pancreatic carcinogenesis by facilitating enhanced tumor growth and survival and are associated with poor prognosis [6,12–14].…”

Section: Introductionmentioning

confidence: 99%

Targeting reactive oxygen species in development and progression of pancreatic cancer

Durand

Störz

2016

Expert Review of Anticancer Therapy

View full text Add to dashboard Cite

Introduction Pancreatic ductal adenocarcinoma (PDA) is characterized by expression of oncogenic KRas which drives all aspects of tumorigenesis. Oncogenic KRas induces the formation of reactive oxygen species (ROS) which have been implicated in initiation and progression of PDA. To facilitate tumor promoting levels and to avoid oncogene-induced senescence or cytotoxicity, ROS homeostasis in PDA cells is balanced by additional up-regulation of antioxidant systems. Areas Covered We examine the sources of ROS in PDA, the mechanisms by which ROS homeostasis is maintained, and the biological consequences of ROS in PDA. Additionally, we discuss the potential mechanisms for targeting ROS homoeostasis as a point of therapeutic intervention. An extensive review of the relevant literature as it relates to the topic was conducted using PubMed. Expert Commentary Even though oncogenic mutations in the KRAS gene have been detected in over 95% of human pancreatic adenocarcinoma, targeting its gene product, KRas, has been difficult. The dependency of PDA cells on balancing ROS homeostasis could be an angle for new prevention or treatment strategies. These include use of antioxidants to prevent formation or progression of precancerous lesions, or methods to increase ROS in tumor cells to toxic levels.

show abstract

“…Activation of the oncogene KRAS signals pancreatic cells to undergo acinar-to-ductal metaplasia, an essential step in the formation of premalignant lesions, which together with the inactivation of tumor suppressor genes, such as CDKN2A, TP53 , and SMAD4 , allow the progression of premalignant lesions to invasive cancer (4). As the activating mutation in the KRAS oncogene is almost systematically associated with PDAC, its role in cancer development has been the subject of numerous studies (5). …”

Section: Pancreatic Ductal Adenocarcinomamentioning

confidence: 99%

Autophagy Induced during Pancreatitis Promotes KRAS-Dependent Transformation in the Pancreas

Iovanna

2016

Front. Oncol.

View full text Add to dashboard Cite

Pancreatitis is an inflammatory disease that both facilitates and accelerates the transformation of pancreatic cells upon activation of the KRAS oncogene. Autophagy is proposed to be one of the cellular mechanisms contributing to pancreatic carcinogenesis, especially during initial stages in which the KRAS oncogene appears to play a key role. Autophagy is also strongly induced during pancreatitis by the overexpression of VMP1. We recently developed a genetically engineered mouse model in which the VMP1 protein is induced simultaneously with the activation of the oncogene KrasG12D specifically in the pancreas, by the addition of doxycycline to a water drink. Using this sophisticated animal model, we can affirm that pancreatic autophagy, induced during pancreatitis by the overexpression of VMP1, promotes the development of precancerous lesions when induced by the mutated KRAS. In addition, the treatment of these mice with chloroquine, an inhibitor of autophagic flux, reverses the effects of VMP1 in pancreatic cancer induced by the KRAS oncogene. Overall, these results bear both mechanistic and biomedical relevance for further understanding and potentially targeting pathways that are critical for initiating pancreatic carcinogenesis, particularly if associated with pancreatitis.

show abstract

Kirsten Ras* oncogene: Significance of its discovery in human cancer research

Cited by 66 publications

References 140 publications

NASA GeneLab Platform Utilized for Biological Response to Space Radiation in Animal Models

NASA GeneLab Platform Utilized for Biological Response to Space Radiation in Animal Models

Targeting reactive oxygen species in development and progression of pancreatic cancer

Autophagy Induced during Pancreatitis Promotes KRAS-Dependent Transformation in the Pancreas

Contact Info

Product

Resources

About