Melanoma epidemiology, biology and prognosis

Ali, Zohra; Yousaf, Nadia; Larkin, James

doi:10.1016/j.ejcsup.2013.07.012

Cited by 218 publications

(188 citation statements)

References 178 publications

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“…Melanoma is still one of the most life‐threatening types of cancer, with an increasing number of incident cases worldwide . Exact knowledge of its cause is the basis for disease prevention, particularly for those at high risk.…”

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confidence: 99%

Characterization of patients at high risk of melanoma in Austria

et al. 2016

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confidence: 99%

Characterization of patients at high risk of melanoma in Austria

et al. 2016

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“…Embryologically, precursor melanocytes are derived from the neural crest and then migrate to different areas in the body, such as the skin, meninges, mucous membranes, upper esophagus, and eyes, during the course of fetal development [9, 10]. Melanoma may arise from any of these peripheral sites, though the most common location is by far hair follicle-bearing skin, arising from melanocytes at dermal-epidermal junctions [11].…”

Section: Introductionmentioning

confidence: 99%

Tropomyosin-Related Kinase Receptor and Neurotrophin Expression in Cutaneous Melanoma Is Associated with a Poor Prognosis and Decreased Survival

et al. 2019

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Objective: Normally, activation of tropomyosin-related kinase (TRK) receptors by neurotrophins (NTs) stimulates intracellular pathways involved in cell survival and proliferation. Dysregulation of NT/TRK signaling may affect neoplasm prognosis. Data on NT and TRK expression in melanomas are limited, and it is unclear whether NT/TRK signaling pathways are involved in the origin and progression of this neoplasm. Methods: We examined whether NT/TRK expression differs across different cutaneous melanoma grades and subtypes, and whether it is associated with melanoma prognosis and survival. A cross-sectional study was performed in which the expression of TrkA, TrkB, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) was analyzed by immunohistochemistry of 154 melanoma samples. We investigated NT/TRK expression associations with prognostic factors for melanoma, relapse-free survival (RFS), and overall survival (OS). Results: Of the 154 melanoma samples, 77 (55.4%) were TrkA immunopositive, 81 (58.3%) were TrkB immunopositive, 113 (81.3%) were BDNF immunopositive, and 104 (75.4%) were NGF immunopositive. We found NT/TRK expression associated strongly with several clinical prognostic factors, including the tumor-node-metastasis stage (p < 0.001), histological subtype (p < 0.001), and Clark level (p < 0.05), as well as with a worse OS (p < 0.05 for all, except TrkB) and RFS (p < 0.05 for all). Conclusions: Our results show strong associations of NT/TRK expression with melanoma stage progression and a poor prognosis.

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“…ICMT catalyzes RAS terminal methylation on the ER membrane, needed to address RAS to the plasma membrane (40)(41)(42). One third of cutaneous melanoma are mutated in RAS, PI3 kinase or other partners of this signaling pathway (5,6). However here, we showed that PFKFB4 promoted RAS signaling and cell migration in two cell lines with wild-type NRAS.…”

Section: Discussionmentioning

confidence: 70%

“…The numerous genetic alterations involved in cutaneous melanoma development can be classified into four subtypes: BRAF, RAS (N/H/K), NF1 and Triple-WT (5). The mitogen-activated protein kinase (MAPK) pathway is the most frequently altered with about 50% of tumors mutated in BRAF gene, followed by about 25% with mutations in NRAS and 14% in NF1, leaving about 10% of the tumors with no identified driver mutation and more complex genetic landscapes (5,6). Although RAS signaling acts upstream of both MAPK and PI3K/AKT signaling (7), it is interesting to note that the two main NRAS activating mutations in cutaneous melanoma, the hotspots Q61 (80% of NRAS subtype tumors) and G12 (15%) drive a different activation of the downstream pathways with preferential activation of MAPK or PI3K/AKT respectively, suggesting a complex modulation of the structure and activity of oncogenic proteins (8,9).…”

Section: Introductionmentioning

confidence: 99%

The glycolysis regulator PFKFB4 interacts with ICMT and activates RAS/AKT signaling-dependent cell migration in melanoma

Sittewelle

Lécuyer

Monsoro-Burq

2020

Preprint

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Cell migration is a complex process, tightly regulated during embryonic development and abnormally activated during cancer metastasis. RAS-dependent signaling is a major nexus controlling essential cell parameters such as proliferation, survival and migration using downstream effectors among which the PI3K/AKT signaling. In melanoma, oncogenic mutations frequently enhance RAS, PI3K/AKT or MAP kinase signaling, in addition to other cancer hallmarks including the activation of metabolism regulators such as PFKFB4, a critical regulator of glycolysis and Warburg effect. Here, we explore a novel function of PFKFB4 in melanoma cell migration. We find that instead of acting as a kinase as recorded in glycolysis, PFKFB4 interacts with ICMT, a post-translational modifier of RAS. PFKFB4 promotes ICMT/RAS interaction, controls RAS addressing at the plasma membrane, activates AKT signaling and enhances cell migration. We thus evidence a novel glycolysis-independent function of PFKFB4 in human cancer cells. This unconventional activity links the metabolic regulator PFKFB4 to RAS-AKT signaling and impacts melanoma cell migration.Highlights.-PFKFB4, a known regulator of glycolysis, displays an unconventional role in melanoma cell migration.-PFKFB4 interacts with ICMT by protein-protein interactions and promotes RAS addressing at the plasma membrane.-PFKFB4 and ICMT cooperation modulates AKT signaling and controls melanoma cell migration.

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Melanoma epidemiology, biology and prognosis

Cited by 218 publications

References 178 publications

Characterization of patients at high risk of melanoma in Austria

Characterization of patients at high risk of melanoma in Austria

Tropomyosin-Related Kinase Receptor and Neurotrophin Expression in Cutaneous Melanoma Is Associated with a Poor Prognosis and Decreased Survival

The glycolysis regulator PFKFB4 interacts with ICMT and activates RAS/AKT signaling-dependent cell migration in melanoma

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