2022
DOI: 10.3390/cells11142183
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Crucial Role of Oncogenic KRAS Mutations in Apoptosis and Autophagy Regulation: Therapeutic Implications

Abstract: KRAS, one of the RAS protein family members, plays an important role in autophagy and apoptosis, through the regulation of several downstream effectors. In cancer cells, KRAS mutations confer the constitutive activation of this oncogene, stimulating cell proliferation, inducing autophagy, suppressing apoptosis, altering cell metabolism, changing cell motility and invasion and modulating the tumor microenvironment. In order to inhibit apoptosis, these oncogenic mutations were reported to upregulate anti-apoptot… Show more

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Cited by 35 publications
(12 citation statements)
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References 154 publications
(303 reference statements)
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“…Oncogenic KRAS mutations confer constitutive activation of MAPK/ ERK and PI3K signals, leading to increased cell proliferation, survival, migration, and invasion, which is associated with a poor prognosis in CRC patients. 16 However, we did not find an advanced malignant phenotype in Apc Δ716 Kras G12D compound mouse tumors. 17 Rather, the Kras mutation significantly increased the number of intestinal adenomatous polyps.…”
Section: Malignant Progression By the Combination Of Kras And Trp53 G...contrasting
confidence: 64%
“…Oncogenic KRAS mutations confer constitutive activation of MAPK/ ERK and PI3K signals, leading to increased cell proliferation, survival, migration, and invasion, which is associated with a poor prognosis in CRC patients. 16 However, we did not find an advanced malignant phenotype in Apc Δ716 Kras G12D compound mouse tumors. 17 Rather, the Kras mutation significantly increased the number of intestinal adenomatous polyps.…”
Section: Malignant Progression By the Combination Of Kras And Trp53 G...contrasting
confidence: 64%
“…Hence, inhibition of the mevalonate pathway disrupts the prenylation of KRAS, and therefore inhibits KRAS activity ( Nam et al, 2021 ). In addition, inhibition of cholesterol synthesis also directly affects the membrane localization of lipophilic proteins like RAS by impeding the dynamic assemblies of sphingolipids, cholesterol, and other components into “lipid rafts” ( Ferreira et al, 2022 ; Yeagle, 2022 ), which suggests the possibility that rosuvastatin prevents KRAS protein from membrane anchoring and suppresses its downstream signaling pathway activation. In addition, it has been reported that statins can uphold reactive oxygen species (ROS) production by curbing the mevalonate pathway, consequently suppressing activation of Akt and ERK pathways ( Qi et al, 2013 ).…”
Section: Discussionmentioning
confidence: 99%
“…1−3 For example, the mutations of the KRAS oncogene have the potential to transform normal cells into cancerous cells, especially for the one-base mismatched single nucleotide polymorphism. 4,5 KRAS is one of the most commonly mutated oncogenes and has been associated with the occurrence of multiple cancers worldwide; for example, its relevant mutations have been found in 35−40% of colorectal cancers, 25% of lung cancers, and 90% of pancreatic cancers. 6,7 Therefore, great efforts have been devoted to developing reliable tactics to differentiate mutant from wild-type (WT) genes.…”
Section: ■ Introductionmentioning
confidence: 99%
“…Aberrant deoxyribonucleic acid (DNA) base alteration, also known as DNA mutation, is a significant hallmark for early diagnosis of diseases including cancer. For example, the mutations of the KRAS oncogene have the potential to transform normal cells into cancerous cells, especially for the one-base mismatched single nucleotide polymorphism. , KRAS is one of the most commonly mutated oncogenes and has been associated with the occurrence of multiple cancers worldwide; for example, its relevant mutations have been found in 35–40% of colorectal cancers, 25% of lung cancers, and 90% of pancreatic cancers. , Therefore, great efforts have been devoted to developing reliable tactics to differentiate mutant from wild-type (WT) genes. , At present, most approaches rely on the polymerase chain reaction (PCR) and sequencing. PCR requires strictly controlled parameters (e.g., temperature cycle, concentrations, primer design, the influence of PCR inhibitors) and prior knowledge of the target sequence.…”
Section: Introductionmentioning
confidence: 99%