IndraLab

Statements

NRAS activates KRAS. 14 / 14
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"Importantly, while inactivation of Hras or Nras increased the growth of oncogenic KRAS-driven lung tumors, inactivation of Hras or Nras had no effect on the growth of oncogenic BRAF-driven lung cancer (Figure 6g, Extended Data Figure 10)."
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"The pan-RAS degrader led to degradation of KRAS, HRAS, and NRAS, whereas the KRAS degrader only depleted KRAS, demonstrating that bioPROTACs can achieve isoform specificity."
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"This rebound, characterized by marked induction of GTP-bound forms of wild-type HRAS and KRAS, which was otherwise abrogated by the knockdown of HRAS and NRAS, leads to MAPK pathway activation in a KRAS G12C-independent way, suggesting that it can not be overcome by escalating the dosage of KRAS G12C inhibitors."
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"In contrast to nonresistant cells, NRAS inhibition alone was sufficient to significantly impair proliferation in resistant cells, and NRAS knockdown only slightly and nonsignificantly induced KRAS upregulation."
30685691
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"Noteably, NRAS knockdown further enhanced inhibition of proliferation in the absence of KRAS (XREF_FIG D)."
30685691
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"It is also possible that NRAS may activate different signaling pathways to KRAS and HRAS; an idea supported by the observation that NRAS has greater transforming activity than KRAS in experimental models of melanoma."
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"But this ras protein is the product of K-ras and H-ras genes rather than N-ras."
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"Ras has four subtypes viz; Ha-Ras, N-Ras, KiRas 4A and KiRas 4B of which KiRas strongly activates MAPK pathway whereas HaRas more strongly activates PI3K and Akt pathway."
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"Such Raichu-KRas probe has been recently used to document the specific activation of K-Ras but not H-Ras or N-Ras on late endosomes thus identifying a mechanism for intracellular signal propagation [XREF_BIBR]."
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"Taken together, these results show that signaling by H-Ras and N-Ras, but not K-Ras, are required to promote PGA 1 -induced apoptosis."
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"Our in vitro data demonstrated that the endogenous mut N-Ras (lung) and H-Ras (bladder) also stimulate the promoter as well as mut K-Ras in pancreatic cancer (Figure 3 and Supplementary Table S1A)."
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"Within cancer signaling, RAF1 is another obligate RAS effector whose gene effect was a mixture of activated NRAS and activated KRAS, as reflected by the UMAP embedding ( xref ) and loadings ( xref )."
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"This therapeutic concept could also be extended to NRas/BRaf-driven melanomas, BRaf-driven pediatric brain tumors, PTEN-driven prostate cancers and KRas-driven NSCLCs that are all Ras/Raf driven malignancies that rely on autophagy for survival (Lee et al., 2019; Mulcahy Levy et al., 2017; Santanam et al., 2016; Strohecker et al., 2013; Xie et al., 2015)."
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"We evaluated the efficiency of Kras deletion and oncogenic Nras activation in Kras ; Nras thymocytes on day 37."
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