Comparative mRNA/micro-RNA co-expression network drives melanomagenesis by promoting epithelial–mesenchymal transition and vasculogenic mimicry signaling

He, Wenfeng; Ye, Gang; Liu, Shuya; Maghsoudloo, Mazaher; Shasaltaneh, Marzieh Dehghan; Kaboli, Parham Jabbarzadeh; Zhang, Cuiwei; Zhang, JingHeng; Entezari, Maliheh; Imani, Saber; Wen, Qinglian

doi:10.1016/j.tranon.2021.101237

Cited by 8 publications

(10 citation statements)

References 83 publications

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“…The results of the present study represented that DMKN levels gradually elevated during the progression of melanomagenesis, while negative DMKN expression predicted an optimistic pancreatic cancer clinical stage [ 7 ]. Additionally, the upregulation of DMKN in the advanced metastatic melanoma tissues could be an excellent diagnostic marker in BRAF/NRAS-driven melanomagenesis [ 11 ].…”

Section: Discussionmentioning

confidence: 95%

“…Additionally, the upregulation of DMKN in the advanced metastatic melanoma tissues could be an excellent diagnostic marker in BRAF/NRAS-driven melanomagenesis [ 11 ]. Interestingly, dmkn genes served as the novel oncogenes triggering VM and EMT processes during the melanomagenesis [ 7 , 11 ]. These results introduced the dmkn genes as a potential VM+EMT network-based diagnostic biomarker to distinguish melanoma patients with high sensitivity and specificity [ 7 , 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is now widely accepted that epithelial-mesenchymal-transition (EMT) is the main pathway during the switching of melanocytes between differentiated and invasive states, resulting in a high rate of metastasis and drug resistance [ 6 ]. Our pan-analyzing of melanoma samples by large-scale weighted gene co-expression network classified that during melanomagenesis, up-regulation of EMT- transcription factors contribute to vasculogenic mimicry (VM)-forming process, resulting in the resistance of anti-angiogenic and anti-vascular therapies for malignant tumor endothelial cells [ 7 , 8 ]. Therefore, transcriptome profiling of EMT/VM-mediated therapeutic resistance samples could be a valuable strategy for finding exceptional responders for the personalized melanoma therapy [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways

Maghsoudloo

et al. 2023

PLoS ONE

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To discover vulnerabilities associated with dermokine (DMKN) as a new trigger of the epithelial-mesenchymal transition (EMT) -driven melanoma, we undertook a genome-wide genetic screening using transgenic. Here, we showed that DMKN expression could be constitutively increased in human malignant melanoma (MM) and that this correlates with poor overall survival in melanoma patients, especially in BRAF-mutated MM samples. Furthermore, in vitro, knockdown of DMKN inhibited the cell proliferation, migration, invasion, and apoptosis of MM cancer cells by the activation of ERK/MAPK signaling pathways and regulator of STAT3 in downstream molecular. By interrogating the in vitro melanoma dataset and characterization of advanced melanoma samples, we found that DMKN downregulated the EMT-like transcriptional program by disrupting EMT cortical actin, increasing the expression of epithelial markers, and decreasing the expression of mesenchymal markers. In addition, whole exome sequencing was presented with p.E69D and p.V91A DMKN mutations as a novel somatic loss of function mutations in those patients. Moreover, our purposeful proof-of-principle modeled the interaction of ERK with p.E69D and p.V91A DMKN mutations in the ERK-MAPK kinas signaling that may be naturally associated with triggering the EMT during melanomagenesis. Altogether, these findings provide preclinical evidence for the role of DMKN in shaping the EMT-like melanoma phenotype and introduced DMKN as a new exceptional responder for personalized MM therapy.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways

Maghsoudloo

et al. 2023

PLoS ONE

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“…Although no previous studies have established a link between DMKN and skin pigmentation, it is noteworthy that mutations in the DMKN gene are implicated in the development of MM via the ERK/MAPK signalling pathways [ 20 ]. Moreover, DMKN microRNAs have emerged as potentially promising biomarkers for diagnosing and treating MM [ 30 ]. Based on these insights, we advocate for further research into the interplay between DMKN and the risk of MM in APs.…”

Section: Discussionmentioning

confidence: 99%

Skin biophysical parameters and serum dermokine levels in airline pilots: a comparative study with office workers

Minoretti,

Sáez,

Martín

et al. 2023

pdia

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Introduction Concerns are growing in the aviation industry about occupational skin diseases like malignant melanoma (MM) among airline pilots (APs), due to the unique working environment that exposes them to various skin stressors. Aim To compare five skin biophysical parameters in a group of 40 male APs, each matched in terms of age and service tenure (minimum of 5 years) with a control group of 40 male office workers (OWs). Considering the potential role of dermokine (DMKN) in skin barrier dysfunction and the pathogenesis of MM, we further analyzed the serum levels of this molecule and correlated them with the measured skin parameters. Material and methods Stratum corneum skin hydration, transepidermal water loss (TEWL), sebum content, erythema index (EI), and melanin index (MI) were quantified by non-invasive instruments in the cheek region. Serum DMKN levels were measured using a commercially available enzyme-linked immunosorbent assay kit. Results Compared with OWs, the skin of APs exhibited a decrease in hydration levels in the stratum corneum, coinciding with a higher TEWL. However, there was no significant variance in sebum content between the groups. MI was notably higher in APs than in OWs, as was EI. In APs, serum DMKN levels were independently associated with MI (β = 0.56, p < 0.05). Conclusions We found a significant link between the profession of an airline pilot and changes in skin biophysical parameters. Further research into the interplay between serum DMKN levels and the risk of MM in APs is warranted.

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“…Being a capacity of the tumour to provide by itself sufficient blood supply for its sustainment [20], VM refers to the ability of aggressive cancer cells to produce fluid-conducting vessel-like structures in an EC-independent way [21]. First discovered in uveal melanoma in 1999 [20], during the following 20 years, VM has been reported in several malignant tumours, including melanoma [22,23], glioblastoma [24,25], osteosarcoma [26,27], hepatocellular carcinoma [28,29], and breast [30,31], lung [32,33], gastric [19,34], colorectal [35,36] and prostate [37,38] cancers. VM is associated with a high tumour grade, invasion, metastasis and poor prognosis in patients with malignant tumours [39][40][41][42][43], including breast [44], colorectal [36], prostate [45], hepatocellular [46], lung [45], ovarian [47], gastric [48] and bladder [49] cancers.…”

Section: Introductionmentioning

confidence: 99%

Physicochemical aspects of the tumour microenvironment as drivers of vasculogenic mimicry

Andreucci

Peppicelli

Ruzzolini

et al. 2022

Cancer Metastasis Rev

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Tumour vascularisation is vital for cancer sustainment representing not only the main source of nutrients and oxygen supply but also an escape route for single or clustered cancer cells that, once detached from the primary mass, enter the blood circulation and disseminate to distant organs. Among the mechanisms identified to contribute to tumour vascularisation, vasculogenic mimicry (VM) is gaining increasing interest in the scientific community representing an intriguing target for cancer treatment. VM indeed associates with highly aggressive tumour phenotypes and strongly impairs patient outcomes. Differently from vessels of healthy tissues, tumour vasculature is extremely heterogeneous and tortuous, impeding efficient chemotherapy delivery, and at the meantime hyperpermeable and thus extremely accessible to metastasising cancer cells. Moreover, tumour vessel disorganisation creates a self-reinforcing vicious circle fuelling cancer malignancy and progression. Because of the inefficient oxygen delivery and metabolic waste removal from tumour vessels, many cells within the tumour mass indeed experience hypoxia and acidosis, now considered hallmarks of cancer. Being strong inducers of vascularisation, therapy resistance, inflammation and metastasis, hypoxia and acidosis create a permissive microenvironment for cancer progression and dissemination. Along with these considerations, we decided to focus our attention on the relationship between hypoxia/acidosis and VM. Indeed, besides tumour angiogenesis, VM is strongly influenced by both hypoxia and acidosis, which could potentiate each other and fuel this vicious circle. Thus, targeting hypoxia and acidosis may represent a potential target to treat VM to impair tumour perfusion and cancer cell sustainment.

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Comparative mRNA/micro-RNA co-expression network drives melanomagenesis by promoting epithelial–mesenchymal transition and vasculogenic mimicry signaling

Cited by 8 publications

References 83 publications

Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways

Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways

Skin biophysical parameters and serum dermokine levels in airline pilots: a comparative study with office workers

Physicochemical aspects of the tumour microenvironment as drivers of vasculogenic mimicry

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