RAF proteins exert both specific and compensatory functions during tumour progression of NRAS-driven melanoma

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RAF proteins exert both specific and compensatory functions during tumour progression of NRAS-driven melanoma

NRAS and its effector BRAF are frequently mutated in melanoma. Paradoxically, CRAF but not BRAF was shown to be critical for various RAS-driven cancers, raising the question of the role of RAF proteins in NRAS-induced melanoma. Here, using conditional ablation of Raf genes in NRAS-induced mouse melanoma models, we investigate their contribution in tumour progression, from the onset of benign tu...

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NRAS and BRAF mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression.

PURPOSE Recently, it was reported that BRAF mutations are frequent in melanoma. Previously, we analyzed a large series of paired primary and metastatic melanomas for NRAS codon 61 mutations and showed that they arise early and are preserved during tumor progression. Here, we have screened the same tumor samples for BRAF mutations. EXPERIMENTAL DESIGN Primary melanomas (n = 71) and correspondi...

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NRAS mutant melanoma – undrugable?

Mutations in the three rat sarcoma (RAS) family members NRAS (neuroblastoma-RAS), HRAS (Harvey-RAS) and KRAS (Kirsten-RAS) are found in one third of human cancers. Among the first oncogenes discovered in cutaneous melanoma was NRAS, which is mutant in up to 20% of tumors causing aberrant signaling in several downstream cascades. Despite, being a highly relevant therapeutic target, design of sma...

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Demonstration of a Melanoma-Specific CD44 Alternative Splicing Pattern That Remains Qualitatively Stable, but Shows Quantitative Changes during Tumour Progression

The role of CD44 in the progression of human melanoma has mostly been characterised by qualitative changes in expression of its individual variable exons. These exons however, may be expressed to form a number of molecules, the alternative splice variants of CD44, which may be structurally and functionally different. Using real-time PCR measurements with variable exon specific primers we have d...

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Targeting mutant (V600E) B-Raf in melanoma interrupts immunoediting of leukocyte functions and melanoma extravasation.

Polymorphonuclear neutrophils (PMN) facilitate melanoma cell extravasation under dynamic flow conditions by the binding of intercellular adhesion molecule-1 (ICAM-1) on melanoma cells to beta2 integrins on PMNs, which is mediated by endogenously produced chemokine interleukin 8 (IL-8) from the tumor microenvironment. However, little is known about the role of B-Raf, the most mutated gene in mal...

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ژورنال

عنوان ژورنال: Nature Communications

سال: 2017

ISSN: 2041-1723

DOI: 10.1038/ncomms15262