A slow-cycling subpopulation of melanoma cells with highly invasive properties

Perego, Michela; Maurer, Margarita; Wang, J X; Shaffer, Sydney M.; Müller, André C.; Parapatics, Katja; Li, L; Hristova, Denitsa M.; Shin, Sally; Keeney, Frederick; Liu, Shujing; Xu, Xiaowei; Raj, Arjun; Jensen, Jan K.; Bennett, Keiryn L.; Wagner, Stephan N.; Somasundaram, Rajasekharan; Herlyn, Meenhard

doi:10.1038/onc.2017.341

Cited by 72 publications

(78 citation statements)

References 72 publications

(68 reference statements)

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“…The high heterogeneity of the tumor cells and their plasticity lead to the possibility that the same drug might induce the switch to slow-cycling resistant phenotype associated to high melanocyte inducing transcription factor levels and to a mesenchymal-like phenotype [42][43][44][45][46] . Early adaptation involving transcriptome reprogramming seems to be particularly relevant even at long time scale, allowing the tumor to survive until a genetic mutation and permanent resistance mechanism is acquired [43,47] .…”

Section: Genetic and Epigenetic Mechanisms Of Resistancementioning

confidence: 99%

Cancer stem cells, plasticity, and drug resistance

Lionetti¹,

Fumagalli²,

Porta³

2020

CDR

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Melanoma is a highly aggressive tumor and almost always fatal when metastatic. Herein, we discuss recent findings on the mechanisms of resistance of human cutaneous melanoma. To achieve a precision medicine approach, the heterogeneity and plasticity of tumor cells are two crucial aspects to be investigated in depth. In fact, to understand the mechanisms that cells use to acquire a resistant phenotype after chemotherapy or how resistant cells inside the tumor are selected, it is the most important issue for a successful therapy. Since new therapeutic strategies are trying to go in this direction, we discuss here the state of the art of the research and the clinical impact of these strategies. We also discuss and suggest future research directions to develop approaches able to define the best concentration and time of exposure of the drug or the cocktails of drugs for each specific patient based on his/her biological features.Melanoma arises from mutated melanocytes, the pigment producing cells. Although melanoma is a rare tumor, occurring in about 1% of all skin malignant tumors, it represents almost 2% of all cancer deaths worldwide [1] ; the survival rate is strictly related to the stage of the tumor and thus to the ability to perform

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Section: Genetic and Epigenetic Mechanisms Of Resistancementioning

confidence: 99%

Cancer stem cells, plasticity, and drug resistance

Lionetti¹,

Fumagalli²,

Porta³

2020

CDR

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“…For example, the C-terminal region of zinc finger III in EGR4 directly interacts with the NF-κB family member p65, leading to robust activation of the IL-2 promoter [89]. There is also growing evidence of a Ca 2+ -dependent feedback loop between NF-κB and STIM1/Orai1 expression in which 1) SOCE drives IκB degradation [90], 2) Ca 2+ regulates NF-κB nuclear localization via p65 S536 phosphorylation [90] and 3) NF-κB is recruited to binding sites in the promoters of STIM1 and Orai1 [91-93]. Since both EGR and NF-κB both regulate STIM1 expression and yet are themselves regulated by Ca 2+ , their co-activation would be expected to be relatively common.…”

Section: Cooperativity Of Transcription Factors In T Cell Activationmentioning

confidence: 99%

EGR-mediated control of STIM expression and function

Gross

Hooper

et al. 2019

Cell Calcium

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Summary Ca2+ is a ubiquitous, dynamic and pluripotent second messenger with highly context-dependent roles in complex cellular processes such as differentiation, proliferation, and cell death [1]. These Ca2+ signals are generated by Ca2+-permeable channels located on the plasma membrane (PM) and endoplasmic reticulum (ER) and shaped by PM- and ER-localized pumps and transporters. Differences in the expression of these Ca2+ homeostasis proteins contribute to cell and context-dependent differences in the spatiotemporal organization of Ca2+ signals and, ultimately, cell fate. This review focuses on the Early Growth Response (EGR) family of zinc finger transcription factors and their role in the transcriptional regulation of Stromal Interaction Molecule (STIM1), a critical regulator of Ca2+ entry in both excitable and non-excitable cells.

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“…Moreover, their expression levels change with the stage of the disease [46]. Importantly, melanoma seems to have the highest mutational load, and once it appeared it becomes life-threatening [47]. Several mutations are frequently linked to cutaneous malignant melanoma, and these mutations are presented in more than 85% of all new diagnosed melanoma cases.…”

Section: Melanoma Biomarkersmentioning

confidence: 99%

“…A recent study reveals a potentially new biomarker, SerpinE2, responsible for the invasive phenotype of melanoma slow-cycling cells. Proteome analysis reports two other proteins enriched in melanoma cells, PDGFRL and BMP1 [47].…”

Section: Melanoma Biomarkersmentioning

confidence: 99%

Mass Spectrometry for Cancer Biomarkers

Albulescu¹,

Petrescu²,

Sârbu³

et al. 2019

Proteomics Technologies and Applications

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Cancer is considered as the second cause of morbidity and also mortality, after cardiovascular diseases. Despite the immense progress in efficacious biomarkers made in the present time, there are very few of them that can timely detect cancers or that can predict treatment outcomes or stratify patients according to their response to the treatment. Among other modern instruments involved in the research of this disease, proteomics emerged strongly, since it analyzes the "molecular effectors." Although it has some setbacks (like the lack of amplification of the signal), it is however one of the best means of investigating the presence and causes and predicting the evolution patterns of the disease. This chapter describes briefly pre-analytical (pre-MS steps), the main concepts, and the MS equipment used for such applications, followed by the presentation of several proteomic applications in melanoma, glioblastoma, pancreatic cancer, and colon cancer.

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A slow-cycling subpopulation of melanoma cells with highly invasive properties

Cited by 72 publications

References 72 publications

Cancer stem cells, plasticity, and drug resistance

Cancer stem cells, plasticity, and drug resistance

EGR-mediated control of STIM expression and function

Mass Spectrometry for Cancer Biomarkers

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