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BRAF-V600E activates ERK. 89 / 90
| 89
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"Our data show that V600E Braf can drive Erk and Wnt pathway activation and the formation of hyperplastic crypts that subsequently remain dormant for prolonged periods due to the upregulation of p16 INK4a."
20941790
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"The BRAF V600E mutation has been shown to activate the MAPK and ERK pathway, and there is evidence of cross-talk between MAPK and ERK signaling and the Wnt pathway in several tumor types, including lung cancer and melanoma [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
29642644
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"We observed similar levels of induced ERK phosphorylation in lysates from cells transfected with cDNAs encoding two well characterized mutants, BRAF V600E and KRAS G12V, known to activate the ERK pathway (XREF_FIG)."
18632602
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"While RAF proteins activate ERK signaling as homo and heterodimers in the presence of active RAS 10, mutant BRAF V600E can activate ERK signaling independent of RAS as an active monomer XREF_BIBR, XREF_BIBR."
32873792
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"The BRAF V600E mutation is a well-accepted poor prognostic factor in patients with metastatic colorectal cancer (mCRC), as it confers Ras-independent stimulation of the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway involved in proliferation, migration, angiogenesis and the suppression of apoptosis."
31353365
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"Induction of ERK1/2 by BRAF V600E was substantially (~ 50%) decreased in KLF9 depleted NHMs or NHMs treated with NAC compared to Vector treated or untreated cells, respectively (XREF_FIG, XREF_FIG)."
30664687
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"In contrast, BGB659, a type II, ATP-competitive RAF inhibitor (compound 27 from Gould et al., 2011), inhibited ERK signaling driven by p61 BRAF V600E dimers and BRAF V600E monomers at similar doses."
26343582
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"Mechanistically, the presence of BRAF V600E mutation activates MEK and ERK signaling and its downstream target RSK."
25679014
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"The dependence of KRAS G12D - and BRAF V600E -expressing PDECs on both the MEK and ERK and PI3K and AKT pathways for survival was unexpected, since BRAF V600E directly stimulates the MEK and ERK signaling cascade, but not the PI3K and AKT pathway."
22871572
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"BRAF V600E is predicted to increase ERK1/2 but not PI 3-kinase --> PDK --> AKT signaling (PI 3-kinase : phosphatidylinositol 3-kinase; PDK : phosphoinositide dependent protein kinase)."
21764747
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"Since RAS activation and CRAF activity are both low in BRAF V600E tumors, in which MEK and ERK signaling is driven almost entirely by BRAF V600E, we hypothesized that the decreased MEK inhibitor sensitivity of KRAS tumors is due to ineffective inhibition of CRAF driven MEK signaling by these drugs."
24746704
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"In parental cells, ERK signaling was inhibited by knockdown of full-length BRAF (V600E) (XREF_SUPPLEMENTARY)."
22113612
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"PLX4032, a selective BRAF (V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells."
23172086
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"Supporting its classification as an oncogene, V600E BRAF stimulates ERK signaling, induces proliferation and is capable of promoting transformation and inducing tumors in transgenic mice."
19010912
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"The BRAF specific inhibitors GDC-0879 and PLX-4720 very efficiently and specifically block BRAF V600E induced ERK activation and xenograft growth [64,65]."
20350535
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"B-RAF V600E mutant protein is constitutively active 51 and earlier studies demonstrated that B-RAF V600E mutant dysregulates NF-kappaB/Snail/RKIP/PTEN circuit as well as activates MEK and ERK kinases that promote the epithelial to mesenchymal transition (EMT) and melanoma cell growth XREF_BIBR, XREF_BIBR."
33707587
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"Accordingly, BRAF V600E transfection in Me1007 melanoma induced a striking ERK1/2 activation followed by c-FOS induction (XREF_FIG e)."
23400877
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"In the current study, we show that BRAF V600E plays a critical role in activating Abl and Arg, which is required for BRAF V600E induction of the EMT transcription factor switch, proliferation and invasion, and Abl and Arg also feedback and potentiate BRAF and ERK signaling."
28368422
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"These results raise the possibility that BRAF V600E cooperated with KRAS G12A to augment the ERK kinase activation, which may also have preference to eosinophil production."
25013473
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"As previously demonstrated, MEK1/2 (PD0325901 and MEKi 1) or BRAF V600E (PLX-4032 and BRAFi 2) inhibition led to decreased P-ERK, P-p70 S6K and P-rpS6 with only modest inhibition of P-4E-BP1."
24425783
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"Indeed, the persistent expression of mutant BRAF was responsible for rebound activation of ERK, as the addition of a BRAF V600E inhibitor or specific knockdown of mutant BRAF inhibited reactivation of ERK after treatment with AUY922."
27391062
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"By contrast, BGB659, a type II, ATP-competitive RAF inhibitor inhibited ERK signaling driven by p61 BRAF V600E dimers and BRAF V600E monomers at similar doses (XREF_FIG and XREF_SUPPLEMENTARY)."
26343582
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"The BRAF gene, a viral oncogene homolog that encodes a kinase involved in the RAS/RAF/MEK/ERK pathway, is mutated in up to 70% of melanomas, with mutations such as BRAF V600E causing constitutive MEK and ERK activation."
20385032
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"Following the down regulation of ALK RES, a decrease in pERK was detected in presence of PLX4032 while no change was observed in absence of the drug, which was expected since BRAF V600E is not inhibited and activates the ERK1/2 pathway."
30290811
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"Finally, BRAF V600E overexpression activated the MEK and ERK signal pathway in B-CPAP and TPC-1 cells."
30126001
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"In the present report, we further explored the influence of growth conditions on melanoma cells and cell response to treatment with vemurafenib (Zelboraf) targeting V600E BRAF and trametinib (Mekinist) targeting mitogen activated kinase and ERK kinase 1/2 (MEK1/2)."
28829835
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"Of note, sustained activation of ERK signaling by the BRaf V600E allele in mice also resulted in increased Lrp6 phosphorylation in the colonic epithelium."
25500543
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"Specifically, the BRAF V600E mutation, which is the most frequent BRAF mutation in melanoma, stimulates the constitutive activation of the downstream extracellular signal regulated kinase (ERK)."
| PMC
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"Second, AMPK activation is suppressed in melanoma cells carrying the most common BRAF mutation V600E, which induces a constitutively active downstream ERK."
25956158
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"Everolimus treatment disrupts the S6K1-IRS-2 and PI3K negative feedback loop, leading to BRAF V600E dependent activation of ERK and Mcl-1 stabilization in colon cancer cells, which in turn blocks the crosstalk from the death receptor to mitochondria."
27351224
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"We previously studied the BRAF V600E mutation that destabilizes the inactive conformation of the BRAF kinase and consequently induces ERK activation."
26322316
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"PLX4032, a selective BRAF (V600E) kinase inhibitor, activates the ERK pathway and enhances cell migra-tion and proliferation of BRAF melanoma cells."
22241959
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"XREF_BIBR In cancer cells, V600E BRAF stimulates constitutive ERK activity and drives proliferation and survival, thereby providing essential tumor growth and maintenance functions."
20667740
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"In melanoma cells, V600E BRAF leads to MEK and ERK pathway activation with concomitant transcriptional constitutive expression of cyclin-D1 and p27 downregulation in an adhesion independent manner."
21663470
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"Collectively, these data suggest that full-scale activation of ERK1/2 by BRAF V600E requires KLF9 or KLF9 dependent ROS in NHMs."
30664687
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"Second, the constitutive activation of ERK by BRAF V600E could inhibit FoxO3 activation via the ubiquitin-proteasome pathway XREF_BIBR."
21249150
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"Selective inhibition of oncogenic BRAF (V600E) with vemurafenib (PLX4032) suppresses ERK signaling, causes melanoma tumor regression, and increases patient survival [XREF_BIBR]."
25026375
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"Vemurafenib targets the oncogenic mutation BRAF V600E, which drives the MAPK and ERK signaling pathway stimulating cellular proliferation, differentiation, and survival."
30320198
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"Although the BRAF V600E -elicited activation of ERK has been demonstrated to contribute to TERT reactivation by maintaining an active chromatin state, it still remains to be addressed how activated ERK is selectively recruited to mutant TERT promoter."
33483600
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"This BRAF V600E mutation occurs in around 40-50% of melanomas and leads to constitutive activation of the mitogen activated protein kinase and extracellular signal regulated kinase 1/2 (MAPK and ERK) signaling pathway (XREF_FIG)."
34025662
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"Oncogenic RAS and BRAF V600E mutations have been reported to activate the MEK and ERK pathway, resulting in DUSP4 expression upregulation and further ERK1/2 inhibition in colorectal cancer cells."
27143921
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"Indeed, only one of the three putative B-RAF V600E resistance alleles identified by random mutagenesis produced sustained MEK and ERK signaling upon re-expression and challenge with a selective RAF inhibitor, and none engendered pharmacological resistance to drug sensitive B-RAF V600E melanoma cells based on growth inhibition assays."
23737487
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"The BRAF V600E (BRAF+) mutation activates the MAPK and ERK pathway and may confer an aggressive phenotype in papillary thyroid cancer (PTC)."
24094449
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"This input of ERK activation from ERBB3 may be more essential and abundant for cell lines expressing BRAF WT than for those expressing BRAF V600E, which activates ERK constitutively."
25000258
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"This phosphomimetic B-Raf V600E mutation results in constitutively active B-Raf and sustained ERK signaling."
27213454
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"Oncogenic BRAF V600E signals as an active monomer in the absence of active RAS, however, in many tumors BRAF dimers mediate ERK signaling."
32873792
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"Here we show that expression of the endogenous BRAF (V600E) allele in mouse embryonic fibroblasts from conditional knock-in transgenic mice activates ERK1/2, represses the BH3-only protein BIM and protects cells from growth factor withdrawal."
18806830
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"In colon cancer cells, initial reduction in ERK signaling by BRAF V600E inhibitor treatment decreases the phosphatase activity of CDC25C, which in turn results in elevated EGFR phosphorylation [XREF_BIBR]."
26023796
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"PLX4032, a selective BRAF (V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells."
20149136
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"Furthermore, preclinical and clinical evidence suggests that these RAF inhibitors will not be effective in colorectal and thyroid BRAF V600E tumors due to relief of negative feedback and RTK mediated reactivation of ERK signaling."
27523909
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"The highly selective BRAF V600E inhibitor, PLX4032 (vemurafenib), inhibits ERK signaling and cell growth in mutant BRAF melanoma cells, but paradoxically enhances signaling in cells with wild-type BRAF."
29481571
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"Expression of KRAS G12D and BRAF V600E results in activation of the MEK and ERK and PI3K and AKT signaling cascades."
22871572
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"The aforementioned tumor cell lines were chosen because they likely represent two different melanoma subgroups; UCD-Mel-N has an activating mutation, Q61R, at NRAS codon 61 (XREF_SUPPLEMENTARY), whereas A375 displays the BRAF V600E activating mutation, and constitutively active ERK and JNK kinases."
19845874
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"Constitutive activation of the ERK pathway caused by BRAF V600E mutation accompanied by loss of PTEN tumor suppressor is the most common cause of melanomagenesis [XREF_BIBR, XREF_BIBR]."
30100999
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"Supporting its classification as an oncogene, V600E BRAF stimulates ERK signaling, induces proliferation and is capable in model systems of promoting transformation."
18473997
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"In contrast to heterozygous BRAF V600E mutation, homozygous BRAF V600E mutation constitutively activated ERK1/2 even in the absence of serum."
17714762
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"As a result, this oncogenic BRAF V600E is constitutively activated independent of its upstream activator protein-RAS, resulting in increased stimulation of its downstream effector proteins-MEK and ERK via phosphorylation."
28708099
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"For instance, BRAF V600E (a mutant of RAF kinase) prevalently occurs in melanoma and colorectal cancer, driving oncogenic ERK signaling even in the absence of activated RAS [59] ."
35410300
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"V600E BRAF mutation stimulates extracellular signal regulated kinase (ERK) signaling, induces proliferation and is capable of promoting transformation."
18644254
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"However, we demonstrated that ERK activation by BRAF V600E may not be a critical factor determining the apoptotic response."
26194071
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"It is the fact that activation of MAPK and Erk signaling by BRAF V600E mutation controls cell growth and survival in part through epigenetic modification including DNA methylation and histone modification."
28656062
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"Compared to wild type BRAF, BRAF V600E shows around 500-fold higher activity, causing sustained activation of ERK signaling."
21602881
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"Supporting its classification as an oncogene, V600E BRAF stimulates ERK signaling, induces proliferation and is capable of promoting transformation."
21818706
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"We confirmed this in ' RAS-less ' cells 3 in which MEK and ERK signalling was rescued by BRAF (V600E), BRAF (K601E) or NRAS (Q61K) but not by wild-type, G466V/E or D594N/G BRAF (XREF_FIG)."
28783719
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"While activation of ERK1/2 by BRAF V600E in melanoma cells inhibits Wnt and beta-catenin signaling XREF_BIBR, forced expression of BRAF V600E enhances Wnt and beta-catenin signaling in normal melanocytes (XREF_FIG)."
24733413
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"B-RAF V600E induces ERK activity independently of the normal EGFR-Ras signals."
24445437
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"Indeed, while some studies reported that V600E BRAF activated ERK signalling and promoted proliferation of melanoma cell lines [XREF_BIBR - XREF_BIBR], other data indicated that the presence of mutant BRAF had no impact on the distant metastasis-free survival in melanoma patients [XREF_BIBR]."
30159130
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"Moreover, BRAF (V600E and R509H) fully activated ERK signaling when expressed in either BRAF-null or ARAF and CRAF-null MEFs (XREF_SUPPLEMENTARY)."
22113612
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"We determined that a full-scale activation of ERK1/2 by BRAF V600E in melanocytes requires KLF9 dependent ROS."
30664687
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"In this manner, B-RAF V600E stimulates extracellular signal regulated kinase (ERK) signaling leading to increased cell proliferation and survival."
21478267
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"We found that BRAF V600E can upregulate anti-apoptotic MCL-1 in a gene dose dependent manner using colorectal cancer cell lines isogenic for BRAF BRAF V600E -induced MCL-1 upregulation was confirmed by ectopic BRAF V600E expression that activated MEK and ERK signaling to phosphorylate (MCL-1 Thr163) and stabilize MCL-1."
27765849
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"Similarly, BRAF V600E mutation results in activation of the MAPK/ERK pathway and is highly associated with poorly differentiated CRCs (5–8) and poor prognosis in microsatellite stable CRC (9)."
31545494
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"Targeting of BRAF V600E decreases downstream activation of MEK and ERK and upregulates expression of melanoma antigens such as MART-1 and gp100 [XREF_BIBR]."
28131904
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"Although BRAF V600E inhibition led to decreased P-ERK1/2, there was substantial residual P-ERK1/2 after 24 hours of drug treatment in these cells."
28233937
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"This V600E BRAF variant possesses a markedly higher dimerization property irrespective of RAS status and strongly activates MEK and ERK1/2 in the presence of vemurafenib."
24108405
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"In vitro studies demonstrate that the resistance of BRAF V600E colorectal cancer cell lines is associated with an adaptive mechanism that utilizes intrinsically high levels of phosphorylated EGFR to engage signaling machinery to activate RAS and, consequently, reactivate the ERK1/2 pathway."
24828387
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"Increased ERK activation by Braf V600E expression reduced retraction persistence, (XREF_SUPPLEMENTARY), similar to the Braf V600E -induced reduction in protrusion persistence."
25990957
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"An earlier study revealed that constitutive activation of B-RAF V600E mutant activates the MEK and ERK pathway and enhances melanoma cell proliferation whereas inhibition of the B-RAF V600E mutant by vemurafenib decreases melanoma cell proliferation 58."
33707587
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"We found that the drugs simultaneously disrupt the BRAF V600E driven extracellular signal regulated kinase (ERK) mitogen activated protein kinase (MAPK) activity and the mechanistic target of rapamycin complex 1 (mTORC1) signaling in melanoma cells."
32531927
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"A recent report using mouse models showed that stabilization of beta-catenin signaling was associated to increased Erk activation [XREF_BIBR], which is in agreement with our hypothesis, where BRAF V600E, powerfully enhancing Erk, is associated to repression of DKK1."
23012583
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"The BRAF V600E mutation results in constitutive MEK and ERK activation 6 which should, in turn, induce Mig-6 transcription; however, mutations in RET and PTC, RAS, or NTRK1 may also activate MAPK sign[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
19040996
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"The kinase activity of BRAF V600E is significantly increased and activates ERK activity independently of RAS signaling."
33348922
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"Liu et al. showed that in BRAF V600E CRC models, TNO155, an SHP2 inhibitor, synergized with BRAF and MEK inhibitors by blocking ERK feedback activation by different RTKs."
36117524
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"To rule out that the PDH phosphorylation is an off target effect of the BRAF inhibitor and since BRAF V600E are known to activate ERK1/2 via MEK1, we investigated the involvement of ERK1/2 and MEK1 in mediating PDH-E1alpha phosphorylation in A375 cells."
28595656
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"We have found that V600E Braf induces an immediate wave of Mek and Erk dependent proliferation within intestinal crypts."
20941790
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"Using reporters, single cell transcriptomics and mass cytometry, we observe cell type specific phosphorylation of ERK in response to transgenic KRAS G12V in mouse intestinal organoids, while transgenic BRAF V600E activates ERK in all cells."
31266962
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"The selective BRAF V600E inhibitor (vemurafenib, 10 microM for 24 h) significantly abrogated the constitutive activation of MEK and ERK pathway as observed through the reduction in p-MEK 1/2, a downstream effector of BRAF and an activator of ERK (XREF_FIG)."
33738242
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"Ephrin-A1 stimulation also caused Akt but not Erk1/2 inactivation in several melanoma cell lines expressing the B-Raf V600E mutant, which constitutively activates Erk1/2 (XREF_FIG)."
20837138
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"BRAF V600E inhibition led to decreased P-ERK1/2 at 4 hours, but by 10 hours P-ERK1/2 levels began to increase with a substantial rebound in P-ERK1/2 at 18 hours."
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