How BRAF effect the proliferation of melanoma?
Best insight from top research papers
BRAF plays a crucial role in the proliferation of melanoma, especially in cases where it is mutated. Mutant BRAF, particularly the V600E mutation, leads to constitutive activation of the MAPK/ERK signaling pathway, promoting uncontrolled cell division. This dependency on BRAF is highlighted in BRAF-mutant melanoma cell lines, where ERK2, a downstream effector of BRAF, is essential for gene expression and proliferation, unlike ERK1. Additionally, inhibiting CRM1, a protein involved in nuclear export, synergizes with BRAF inhibitors to impair melanoma survival, regardless of BRAF mutation status, by inducing cell-cycle arrest and apoptosis. In BRAF wild-type melanomas, elevated ERBB4 signaling, often associated with RAS mutations, can drive proliferation through PI3K signaling pathways.
Answers from top 5 papers
More filters
| Papers (5) | Insight |
|---|---|
| ERBB4 drives proliferation in BRAF-WT melanoma cell lines by cooperating with RAS signaling, promoting PI3K signaling, and stimulating clonogenic proliferation, impacting treatment strategies for these melanomas. | |
| A mutation in B‐Raf, particularly V600E, leads to constitutive activity, causing uncontrolled cell division in melanoma, making it a major contributor to B‐Raf mutation-induced melanoma. | |
| ERK2, not ERK1, is crucial for BRAF-mutant melanoma proliferation due to its higher expression. Targeting ERK2 selectively may spare normal tissue toxicity associated with pan-ERK inhibition. | |
| ERK2, not ERK1, is crucial for BRAF-mutant melanoma proliferation due to its higher expression. Targeting ERK2 selectively may spare normal tissue toxicity associated with pan-ERK inhibition. | |
03 Apr 2023 | BRAF inhibition synergizes with CRM1 inhibition to decrease melanoma viability, induce cell-cycle arrest, and enhance apoptosis, ultimately leading to tumor regression in BRAF-mutant melanoma. |
Related Questions
What are the specific genetic mutations associated with the development of melanoma?4 answersSpecific genetic mutations associated with the development of melanoma include mutations in the BRAF gene, such as p.V600E and p.V600K, which are found in up to 95% and 20% of BRAF-mutant melanomas, respectively. Mutations in the NRAS gene, including G12, G13, and Q61 mutations, are also commonly observed in melanoma. In addition to these driver gene mutations, other mutations have been identified in melanoma genomes, including TP53, COL1A1, PPP6C, KALRN, PIK3R4, TRPM6, GUCY2C, and PRKAA2, which are more likely associated with BRAF-driven or NRAS-driven melanomas. Furthermore, a study using multiregion tumor sequencing revealed heterogeneous somatic mutations in individual melanoma tumors, with known mutations in BRAF and NRAS being ubiquitous events. These findings highlight the genetic complexity and heterogeneity of melanoma, providing insights into the underlying genetic aberrations driving tumorigenesis.
What is the effect of radiation on melanogenesis?4 answersRadiation has various effects on melanogenesis. Ultraviolet (UV) radiation, such as UVB and UVA, can stimulate melanin production in the skin. Exposure to UV radiation or α-melanocyte-stimulating hormone (α-MSH) activates the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway, leading to melanin synthesis. However, radiofrequency (RF) irradiation can decrease ATP release from keratinocytes and suppress the expression of factors involved in melanogenesis, such as CD39, CD73, and A2A/A2BARs. Additionally, 5G electromagnetic radiation (EMR) at 28 GHz can attenuate skin pigmentation by reducing ROS generation, which is crucial for melanin synthesis. Furthermore, protracted exposure to X-rays at low dose rates affects the survival and metabolic activity of melanized and non-melanized fungal cells, with melanized cells showing better survival and metabolic profiles. Overall, radiation can both stimulate and inhibit melanogenesis depending on the type and dose of radiation.
What is the effect of retinoids on melanogenesis?5 answersRetinoids have been found to have different effects on melanogenesis depending on the stage of melanocyte differentiation. In earlier stages, retinoids promote differentiation of embryonic stem cells into melanoblasts via neural crest cells, while in later stages, they inhibit differentiation of melanoblasts into melanocytes. Additionally, retinoids have been shown to stimulate constitutive melanogenesis in melanoma cells, but inhibit hormonally or pharmacologically induced melanogenesis in these cells. Furthermore, retinoic acid has been found to increase melanogenesis in B16F10 melanoma cells, leading to an increase in the relative volume of melanosomes and melanin formation. However, the effect of retinoic acid on normal human melanocytes is less clear, with some studies showing inhibition of growth and little effect on melanogenesis. Further research is needed to fully understand the effects of retinoids on melanogenesis in different cell types and conditions.
Cancer stem cells in melanoma5 answersCancer stem cells (CSCs) have been identified in melanoma, characterized by their ability to self-renew, establish tumors, and resist chemotherapy and radiotherapy. These CSCs are responsible for relapse, metastasis, and drug resistance in melanoma. Various markers have been associated with melanoma stem cells, including ALDH1, CD133, ABCB5, CD166, Nestin, BMI-1, and specific signaling pathways such as Wnt, Notch, and Hedgehog. High expression of CSC biomarkers is associated with adverse prognosis in melanoma. Therapeutic strategies targeting CSCs, such as immunotherapy with dendritic cells and anti-CD20 antibody Rituximab, have shown promising results in melanoma treatment. The presence of melanoma stem cells may contribute to tumor heterogeneity, drug resistance, and tumor invasiveness. Further research is needed to better understand the origin, function, and therapeutic potential of melanoma stem cells.
What is the importance of braf mutations in colon cancer?5 answersBRAF mutations in colon cancer are of significant importance. They have been associated with poor survival and controversial treatment strategies. The presence of BRAF mutations in colorectal cancer, particularly the BRAF V600E mutation, has led to the identification of therapeutic opportunities. Recent discoveries have shown that BRAF and MEK inhibition combined with epidermal growth factor receptor-directed therapy can be effective for patients with advanced-stage BRAF V600-mutant colorectal cancer. Additionally, the immune checkpoint inhibitor therapy is more appealing for patients with BRAF V600E-mutant mismatch repair-deficient colorectal cancer. The frequency of BRAF V600E mutations in right-side colon cancer, especially in the cecum, is high. Liquid biopsy has shown promise in detecting BRAF V600E mutations in plasma, particularly in patients with advanced cancer. The significance of BRAF mutations in the development of colorectal cancer has been established, leading to the categorization of BRAF-mutated colorectal cancers as an independent category.
What is importance of braf mutations in colon cancer?5 answersBRAF mutations in colon cancer are of significant importance. Patients with BRAF mutated colon cancer have poor survival outcomes and controversial treatment strategies. The tumor microenvironment in BRAF mutated colon cancer is different, with more stromal cells, immune cell infiltration, and lower tumor purity. Several immunotherapeutic targets, such as PD-1, PD-L1, CTLA-4, LAG-3, and TIM-3, are highly expressed in BRAF mutated patients. BRAF mutation is also associated with higher proportions of neutrophils and macrophages M1, and lower proportions of plasma cells, dendritic cells resting, and T cells CD4 naive. BRAF mutations are observed at high frequency in right-side colon cancer, especially in the cecum, and can be detected in plasma. BRAF mutations in colorectal cancer stratified for molecular background have prognostic and clinical significance. In stage IV CRC, BRAF mutations are an independent negative prognostic factor, but patients with BRAF mutations may have better prognoses if treated with chemotherapy prior to tumor resection.