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KRAS activates angiogenesis. 39 / 39
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"Expression of VEGF and/or of negative regulators of angiogenesis (thrombospondin-1 repression through phosphorylated Myc, hyperactivation of PIK3/Rho pathway) have been reported to be regulated by RAS[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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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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"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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"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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"Mutations in KRAS and BRAF promote cancer progression by enhancing angiogenesis, influencing cell motility and adhesion, and triggering aggressive biological traits in cancer cells20, 21."
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"1 In addition, mutated K-ras promotes angiogenesis and, in turn, helps tumor succession."
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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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"In lung cancer cells, knocking down YY1 greatly suppressed cell migration, proliferation, and angiogenesis mediated by oncogenic KRas (KRas ) [86]."
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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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"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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"KRAS signal activation triggers tumor cell proliferation, invasion, angiogenesis, metastasis, adhesion, and resistance to apoptosis.In order to reduce the progression of tumor cells caused by KRAS mut[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Oncogenic KRAS drives lipo-fibrogenesis to promote angiogenesis and colon cancer progression."
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"Wnt/β-catenin, K-ras/MAPK, IL-1β/NF-κB, etc. have been reported to induce angiogenesis inside CRC milieu via upregulating VEGF [ 62 , 78–80 ]."
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"KRAS signal activation triggers tumor cell proliferation, invasion, angiogenesis, metastasis, adhesion, and resistance to apoptosis."
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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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"Okada F et al. [45] found that RAS-gene mutations could increase KRAS-dependent VEGF expression, promoting tumor angiogenesis and growth."
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"KRAS activation in gastric cancer stem-like cells promotes tumor angiogenesis and metastasis."
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"PMID :11593418 [32] Matsuo Y, Campbell PM, Brekken RA, Sung B, Ouellette MM, Fleming JB, Aggarwal BB, Der CJ, Guha S. K-Ras promotes angiogenesis mediated by immortalized human pancreatic epithelial cells through mitogen activated protein kinase signaling pathways."
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"Targeting oncogenic KRAS in non small cell lung cancer cells by phenformin inhibits growth and angiogenesis."
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"Additionally, blocking anoikis-inducing mechanisms by the anoikis inhibitor K- ras triggers angiogenesis ( Derouet et al. 2007 )."
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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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"Reports suggest that mutations in the K-ras oncogene may contribute to progression of colon cancer by enhancing angiogenesis, invasion, and metastasis of tumors."
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"Knockdown of KRAS decreased levels of HIF-1α, bFGF and VEGF, suggesting that KRAS promotes angiogenesis in CRC [82] ."
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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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"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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"Here we analyze how this KRAS activation in gastric CSCs promotes tumor angiogenesis and metastasis."
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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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"IKKbeta targeting reduces KRAS induced lung cancer angiogenesis in vitro and in vivo : a potential anti-angiogenic therapeutic target."
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"Retraction Note: KRAS activation in gastric cancer stem-like cells promotes tumor angiogenesis and metastasis."
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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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"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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"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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"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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"They identify a molecular signaling cascade downstream of KRAS* that activates a specific program of lipid-rich CAFs, promoting tumor angiogenesis and progression."
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"The STRING database indicates that NRG interacts with EGFR, a receptor protein critical for bone formation (Table 3), as well as with proteins ERBB3, HRAS, HSP90AA1 and KRAS that promote angiogenesis and neovascularization ."
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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 PDAC, the activation of Kras promotes the production of inflammatory cytokines, including IL-1, which activates NF-κB to promote tumor cell survival and proliferation, increased invasive and metastatic behavior, and angiogenesis [5,12,13,14]."
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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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"K-Ras 4A might activate effector pathways that transform cells and enable anchorage-independent growth, whereas K-Ras 4B could promote cell motility and thereby facilitate angiogenesis, invasion and, [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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