Abstract:
:We have recently reported that human melanoma cells express a variety of voltage-gated calcium (Ca(2+) ) channel types, including low-voltage-activated T-type channels that play a significant role in melanoma cell cycle progression. Here, we challenged melanoma metastatic cells with T-type channel blockers of clinical use and found a dual effect on cell viability: (i) a reduction in the proliferation rate, through a halt in the progression to the G1 -S phase; and (ii) a promotion of cell death that was partially dependent on the activation of caspases. An in-depth analysis of the death process showed that the apoptotic pathway is preceded by endoplasmic reticulum stress and the subsequent inhibition of the basal macroautophagy which is active in these cells. The effects of pharmacological blockers on Ca(2+) homeostasis, autophagy, and cell death were mimicked by T-type channel gene silencing. These results provide the basis for a new pharmacological and/or gene silencing approach toward tackling melanoma metastasis.
journal_name
Pigment Cell Melanoma Resjournal_title
Pigment cell & melanoma researchauthors
Das A,Pushparaj C,Herreros J,Nager M,Vilella R,Portero M,Pamplona R,Matias-Guiu X,Martí RM,Cantí Cdoi
10.1111/pcmr.12155subject
Has Abstractpub_date
2013-11-01 00:00:00pages
874-85issue
6eissn
1755-1471issn
1755-148Xjournal_volume
26pub_type
杂志文章abstract::The advent of immune checkpoint blockers and targeted therapies has changed the outcome of melanoma. However, many patients experience relapses, emphasizing the need for predictive and prognostic biomarkers. We developed a strategy based on plasmacytoid dendritic cells (pDCs) loaded with melanoma tumor antigens that a...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12618
更新日期:2018-01-01 00:00:00
abstract::Neurofibromatosis type 1 (NF1) is a frequent genetic disease leading to the development of Schwann cell-derived neurofibromas or melanocytic lesions called café-au-lait macules (CALMs). The molecular mechanisms involved in CALMs formation remain largely unknown. In this report, we show for the first time pathophysiolo...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12369
更新日期:2015-07-01 00:00:00
abstract::The novel mutation named ru2(d) /Hps5(ru2-d) , characterized by light-colored coats and ruby-eyes, prohibits differentiation of melanocytes by inhibiting tyrosinase (Tyr) activity, expression of Tyr, Tyr-related protein 1 (Tyrp1), Tyrp2, and Kit. However, it is not known whether the ru2(d) allele affects pheomelanin s...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12118
更新日期:2013-09-01 00:00:00
abstract::Oncogenic mutations in BRAF are common in melanoma and drive constitutive activation of the MEK/ERK pathway. To elucidate the transcriptional events downstream of (V600E)BRAF/MEK signalling we performed gene expression profiling of A375 melanoma cells treated with potent and selective inhibitors of (V600E)BRAF and MEK...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2009.00618.x
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abstract::Hair color and skin color are frequently coordinated in mammalian species. To explore this, we have studied mutations in two different G protein coupled pathways, each of which affects the darkness of both hair and skin color. In each mouse mutant (Gnaq(Dsk1), Gna11(Dsk7), and Mc1r(e)), we analyzed the melanocyte dens...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2009.00609.x
更新日期:2009-12-01 00:00:00
abstract::The neural crest is a transient structure in vertebrate embryos that generates multiple neural and mesenchymal cell types as well as melanocytes. Melanocytes in the skin either derive directly from neural crest cells populating the skin via a dorsolateral migratory pathway or arise by detaching from nerves innervating...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/j.1755-148X.2011.00834.x
更新日期:2011-06-01 00:00:00
abstract::The Dark brown (DB) mutation in chickens reduces expression of black eumelanin and enhances expression of red pheomelanin, but only in certain parts of the plumage. Here, we present genetic evidence that an 8.3-kb deletion upstream of the SOX10 transcription start site is the causal mutation underlying the DB phenotyp...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2011.00825.x
更新日期:2011-04-01 00:00:00
abstract::Retinoic acid (RA) is considered to control melanocytes; however, its precise mechanism remains unclear because of a bimodal effect, which promotes or inhibits melanin synthesis depending on the cell type, culture condition of melanocytes and skin conditions. In this study, we examined the effects of RA throughout eac...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2012.00988.x
更新日期:2012-05-01 00:00:00
abstract::Oculocutaneous albinism (OCA) is caused by mutations in six different genes, and their molecular diagnosis encompasses the search for point mutations and intragenic rearrangements. Here, we used high-resolution array-comparative genome hybridization (CGH) to search for rearrangements across exons, introns and regulato...
journal_title:Pigment cell & melanoma research
pub_type: 临床试验,杂志文章
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abstract::PMEL is a pigment cell-specific protein responsible for the formation of fibrillar sheets within the pigment organelle, the melanosome. The fibrillar sheets serve as a template upon which melanins polymerize as they are synthesized. The PMEL fibrils are required for optimal pigment cell function, as animals that eithe...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/pcmr.12067
更新日期:2013-05-01 00:00:00
abstract::One of the main advantages of using inducible and conditional transgenes to study pigment cell biology is that they allow for genetic manipulation within melanocytes after roles in general neural crest or melanoblast development have been fulfilled. Specifically, we focus here on the ability of the Tyr::CreER(T) ...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12048
更新日期:2013-03-01 00:00:00
abstract::In response to the dynamic intra-tumor microenvironment, melanoma cells adopt distinct phenotypic states associated with differential expression of the microphthalmia-associated transcription factor (MITF). The response to hypoxia is driven by hypoxia-inducible transcription factors (HIFs) that reprogram metabolism an...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12802
更新日期:2019-11-01 00:00:00
abstract::Melanoma central nervous system metastases are increasing, and the challenges presented by this patient population remain complex. In December 2015, the Melanoma Research Foundation and the Wistar Institute hosted the First Summit on Melanoma Central Nervous System (CNS) Metastases in Philadelphia, Pennsylvania. Here,...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/pcmr.12538
更新日期:2016-11-01 00:00:00
abstract::Oncogenic BRAF mutations are more frequent in cutaneous melanoma occurring at sites with little or moderate sun-induced damage than at sites with severe cumulative solar ultraviolet (UV) damage. We studied cutaneous melanomas from geographic regions with different levels of ambient UV radiation to delineate the relati...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2011.00837.x
更新日期:2011-04-01 00:00:00
abstract::The complex genetic changes underlying metastatic melanoma need to be deciphered to develop new and effective therapeutics. Previously, genome-wide microarray analyses of human melanoma identified two reciprocal gene expression programs, including transcripts regulated by either transforming growth factor, beta 1 (TGF...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12255
更新日期:2014-09-01 00:00:00
abstract::While sunlight is important for life, ultraviolet radiation (UVR) can have harmful and mutagenic effects. This duality is particularly relevant to human skin, in which UVR both participates in evolutionarily important photochemical reactions yet may act as a potential carcinogen. UVR can upregulate production of melan...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/j.1755-148X.2010.00775.x
更新日期:2010-12-01 00:00:00
abstract::Several studies observed that adiponectin, an important adipokine that improves glucose metabolism by regulating AMP-activated protein kinase (AMPK) signaling, is dermatologically beneficial. In our recent microarray data, we found that adiponectin expression was lower in lesional skin than in non-lesional skin of mel...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12596
更新日期:2017-01-01 00:00:00
abstract::Ultraviolet radiation (UVR) can play two roles: induce cellular senescence and convert skin melanocytes into melanoma. To assess whether this conversion might rely on melanocytes having to first acquire a senescent phenotype, we studied the effects of physiological doses of UVR (UVA + UVB) on quiescent melanocytes in ...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12888
更新日期:2020-09-01 00:00:00
abstract::Melanoma is a disease associated with a very high mutation burden and thus the possibility of a diverse range of oncogenic mechanisms that allow it to evade therapeutic interventions and the immune system. Here, we describe the characterization of a panel of 102 cell lines from metastatic melanomas (the NZM lines), in...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12908
更新日期:2021-01-01 00:00:00
abstract::The liver is the organ usually affected by metastatic uveal melanoma (MUM). Current treatments are almost always ineffective and mortality remains high. In this study, copy number variations (CNVs) were identified in 12 metastatic and five matched primary UMs (PUMs). Our data revealed a wide spectrum of genetic altera...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12433
更新日期:2016-01-01 00:00:00
abstract::Metformin is the most widely used antidiabetic drug that belongs to the biguanide class. It is very well tolerated and has the major clinical advantage of not inducing hypoglycemia. Metformin decreases hepatic glucose production via a mechanism requiring liver kinase B1, which controls the metabolic checkpoint, AMP-ac...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
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abstract::From a therapeutic standpoint, vitiligo is still regarded by many physicians as a simple problem of regenerative medicine, with the main aim to repopulate the depigmented skin with functional melanocytes from the margins of the lesions or from intact progenitors in hair follicles. However, recent research in vitiligo ...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/j.1755-148X.2011.00939.x
更新日期:2012-01-01 00:00:00
abstract::Mice lacking the E3 ubiquitin ligase mahogunin ring finger-1 (MGRN1) have a pleiotropic phenotype that includes spongiform neurodegeneration, embryonic patterning defects, and dark fur due to a defect in pigment-type switching. The only MGRN1 ubiquitination target identified to date is tumor susceptibility gene 101 (T...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12059
更新日期:2013-03-01 00:00:00
abstract::Zebrafish respond to visual stimuli to adapt their body colour to the background. If, rather than being a simple on/off reaction to visual stimulation, the colour change involves cognitive and memory-related processes, training fish with cyclical changes of the background would be expected to increase its ability to c...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2008.00445.x
更新日期:2008-06-01 00:00:00
abstract::The Melanoma Research Foundation (MRF) has charted a comprehensive assessment of the current state of melanoma research and care. Intensive discussions among members of the MRF Scientific Advisory Council and Breakthrough Consortium, a group that included clinicians and scientists, focused on four thematic areas - dia...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12475
更新日期:2016-07-01 00:00:00
abstract::BRAF inhibitors improve melanoma patient survival, but resistance invariably develops. Here we report the discovery of a novel BRAF mutation that confers resistance to PLX4032 employing whole-exome sequencing of drug-resistant BRAF(V600K) melanoma cells. We further describe a new screening approach, a genome-wide pigg...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12197
更新日期:2014-03-01 00:00:00
abstract::Many melanoma cells are resistant to the anti-proliferative effect of all trans retinoic acid (ATRA). Retinoic Acid Receptor-beta2 (RAR-beta2) mediates the ATRA growth inhibition. We found a correlation between the anti-proliferative activity of ATRA and expression of RAR-beta2. There was not a strict correlation betw...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2010.00702.x
更新日期:2010-06-01 00:00:00
abstract::Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary genodermatosis caused by mutations in ADAR1. In this study, we performed mutation analysis on a family that included typical DSH patients. No mutations were found in any coding regions or exon-intron boundary regions of ADAR1, but a previously unreported non-...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12863
更新日期:2020-07-01 00:00:00
abstract::Hermansky-Pudlak syndrome (HPS) is a rare recessive disorder characterized by hypopigmentation, bleeding diathesis, and other symptoms due to multiple defects in lysosome-related organelles. Ten HPS subtypes have been identified with mutations in HPS1 to HPS10. Only four patients with HPS-1 have been reported in Chine...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12534
更新日期:2016-11-01 00:00:00
abstract::Mutations within the OCA2 gene or the complete absence of the OCA2 protein leads to oculocutaneous albinism type 2. The OCA2 protein plays a central role in melanosome biogenesis, and it is a strong determinant of the eumelanin content in melanocytes. Transcript levels of the OCA2 gene are strongly correlated with pig...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/pcmr.12210
更新日期:2014-03-01 00:00:00