IndraLab

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KRAS activates angiogenesis. 20 / 20
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"Given our hypothesis that IKKbeta promotes KRAS induced angiogenesis, which relies on KRAS induced VEGF and IL-8 secretion [XREF_BIBR, XREF_BIBR], and given that VEGF and IL-8 are transcriptional targets of NF-kappaB [XREF_BIBR], a transcription factor activated by oncogenic KRAS in the lung in an IKKbeta dependent manner [XREF_BIBR], we decided to investigate whether IKKbeta targeting would affect VEGF and IL-8 expression."
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"Taken together, these results provide a novel mechanistic understanding of how the IKKbeta pathway affects human lung tumorigenesis, indicating that IKKbeta promotes KRAS induced angiogenesis both by cancer cell-intrinsic and cancer cell independent mechanisms, which strongly suggests IKKbeta inhibition as a promising antiangiogenic approach to be explored for KRAS induced lung cancer therapy."
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"K-Ras Promotes Angiogenesis Mediated by Immortalized Human Pancreatic Epithelial Cells through Mitogen Activated Protein Kinase Signaling Pathways."
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"Similar results were obtained using another pair of immortalized human pancreatic duct derived cells, E6/E7/st and its oncogenic K-Ras variant, E6/E7/Ras/st. Taken together, our results suggest that angiogenesis is initiated by paracrine epithelial secretion of CXC chemokines and VEGF downstream of activated oncogenic K-Ras, and that this vascular maturation is in part dependent on MEK1/2 and c-Jun signaling."
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"Taken together, these results suggest that IKKbeta is an important mediator of KRAS induced angiogenesis, and that IKKbeta promotes angiogenesis both by cancer cell dependent and -independent mechanisms."
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"Even though pathological angiogenesis in this model is not induced by KRAS, it can result in activation of the IKK and NF-kappaB pathway due to the relative hypoxia induced by the change in oxygen levels."
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"PDAC often harbors the universal mutations in the proto-oncogene K-RAS (>90% prevalence in pancreatic cancer), which persistently accelerates and activates various oncogenic events (e.g., uncontrolled proliferation, sustained angiogenesis, metastasis, or invasion), thus leading to metabolic reprogramming and resistance to cell death [1, 2]."
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"In conclusion, we have identified IKKbeta as a mediator of KRAS induced angiogenesis in lung cancer in part by promoting secretion of proangiogenic factors VEGF and IL-8."
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"GSEA identified a number of biological states and processes overrepresented in the glioblastoma infiltrating CD14 + cells relative to those in CD14 + blood cells, including signaling by KRAS, TGF-beta, and TNF-alpha; epithelial-mesenchymal transition; angiogenesis; coagulation; the G 2 / M cell cycle checkpoint; and hypoxia (XREF_FIG)."
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"Targeting oncogenic KRAS in non small cell lung cancer cells by phenformin inhibits growth and angiogenesis."
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"Even though other IKKbeta independent pathways may contribute to KRAS induced angiogenesis, our data indicate that IKKbeta is an important mediator of KRAS induced proangiogenic effects."
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"Based on published studies showing that oncogenic RAS promotes angiogenesis by upregulating the proangiogenic NF-kappaB target genes IL-8 and VEGF, that NF-kappaB activation by KRAS requires the IKKbeta kinase, and that targeting IKKbeta reduces KRAS induced lung tumor growth in vivo, but has limited effects on cell growth in vitro, we hypothesized that IKKbeta targeting would reduce lung tumor growth by inhibiting KRAS induced angiogenesis."
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"IKKbeta targeting reduces KRAS induced lung cancer angiogenesis in vitro and in vivo : a potential anti-angiogenic therapeutic target."
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"Therefore, to evaluate whether cancer cell-intrinsic IKKbeta activity is required for KRAS induced angiogenesis in human tumors, we performed xenograft studies with human A549 cells with siRNA mediated IKKbeta silencing."
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"In CRCs, KRAS and PI3K, downstream molecules in the EGF receptor pathway, promote tumor growth, survival, angiogenesis and metastasis [XREF_BIBR]."
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"Given that NF-kappaB activation by KRAS in the lung requires the IKKbeta kinase [XREF_BIBR], and that systemic IKKbeta targeting reduced KRAS induced lung tumor growth [XREF_BIBR], we hypothesized that IKKbeta, which is a druggable target in the KRAS induced NF-kappaB activation pathway, would be involved in mediating KRAS induced angiogenesis."
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"Besides, PI3K-Akt pathway also plays an important role in hematopoiesis and angiogenesis mediated by K-ras signal pathway [XREF_BIBR]."
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"Taken together, our results indicate that IKKbeta promotes KRAS induced angiogenesis by both cancer cell-intrinsic and cancer cell independent mechanisms, which strongly suggests IKKbeta inhibition as a promising antiangiogenic approach to be explored for KRAS induced lung cancer therapy and possibly also for therapy of other KRAS driven malignancies."
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"1 In addition, mutated K-ras promotes angiogenesis and, in turn, helps tumor succession."
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"Interestingly, tumor expression of oncogene k-ras upregulates the pro inflammatory cytokine IL-8, resulting in immune cell infiltration, enlarged tumor and enhanced angiogenesis in colon cancer."
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