BMP Signaling Promotes Neural Crest Identity and Accelerates Melanoma Onset

Gramann, Alec; Frantz, William Tyler; Dresser, Karen; Gomes, Camilla Borges Ferreira; Lian, Christine G.; Deng, April; Ceol, Craig J.

doi:10.1016/j.jid.2021.01.021

Cited by 7 publications

(4 citation statements)

References 14 publications

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“…The tightly connected communication network uncovered the extensive interactions within melanoma, plenty of which are worthy of thorough studies in the future. BMP signaling plays a pivotal role in the regulation of neural crest and melanocyte programs whether in normal or pathological states ( Gramann et al, 2021 ). It has been reported previously that BMP signaling is active in 80% of melanomas, whereas it is inactive in adult differentiated melanocytes ( Gramann et al, 2019 ; Venkatesan et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported previously that BMP signaling is active in 80% of melanomas, whereas it is inactive in adult differentiated melanocytes ( Gramann et al, 2019 ; Venkatesan et al, 2018 ). Recent research has demonstrated that BMP signaling can promote neural crest recognition and accelerate the occurrence of melanoma ( Gramann et al, 2021 ). The activation of BMP signaling can induce Epithelial–mesenchymal transition (EMT), leading to the aggressive phenotype of melanoma ( Gao et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

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Construction and Validation of a Ferroptosis-Related Prognostic Signature for Melanoma Based on Single-Cell RNA Sequencing

Liu

Shou

Zhu

et al. 2022

Front. Cell Dev. Biol.

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Melanoma, the deadliest type of skin cancer, is on the rise globally. The generally poor prognosis makes melanoma still an enormous public health problem. Ferroptosis is a newly emerging form of iron-dependent regulated cell death, which has been implicated in the development and treatment of several tumors. However, whether there is a connection between ferroptosis-related genes and the prognosis of melanoma patients remains an enigma. In the present study, we identified a ferroptosis-related genes signature to predict the prognosis of melanoma patients by analyzing single-cell RNA-sequencing data from the Gene Expression Omnibus (GEO). Single-cell trajectory analysis was performed to explore malignant differentiation. CellChat was used to investigate intercellular communications in melanoma. Collectively, a novel four-gene signature (CP, MAP1LC3A, transferrin, and TP53) was constructed for prognosis prediction. COX proportional hazards regression analysis showed that the established ferroptosis-associated risk model was an independent prognostic predictor for melanoma patients (HR = 2.3293; 95%CI 1.1528–4.706) (p < 0.018). Patients with low-risk scores had significantly better overall survival (OS) than those with high-risk scores in The Cancer Genome Atlas, GSE59455, and GSE22153 dataset (p = 0.0015, p = 0.031, p = 0.077). Furthermore, the gene expression level of the four genes were verified in multistrain melanoma cell lines and normal human epidermal melanocytes (NHEM). The protein expression level of the four genes in clinical samples were further verified in the Human Protein Atlas (HPA) databases. Taken together, our study identified the prognostic significance of the ferroptosis-related genes in melanoma and developed a novel four-gene prognostic signature, which may shed light on the prognostic assessment and clinical decision making for melanoma patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Construction and Validation of a Ferroptosis-Related Prognostic Signature for Melanoma Based on Single-Cell RNA Sequencing

Liu

Shou

Zhu

et al. 2022

Front. Cell Dev. Biol.

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“…BMP signaling is present in 80% of melanomas but is absent in adult melanocytes. A recent study in a zebrafish melanoma model found BMP signaling has a large effect on early progression and contributes to the initiation of melanoma ( 134 ). The impact of BMPs on early progression, pathways controlling EMT, and their prevalence in melanoma specifically highlights the potent effects of NCSC genes.…”

Section: Neural Crest Stem Cell Genes In Emt/metastasis and Immune Es...mentioning

confidence: 99%

Immune escape and metastasis mechanisms in melanoma: breaking down the dichotomy

Shirley,

Chhabra,

Amiri

et al. 2024

Front. Immunol.

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Melanoma is one of the most lethal neoplasms of the skin. Despite the revolutionary introduction of immune checkpoint inhibitors, metastatic spread, and recurrence remain critical problems in resistant cases. Melanoma employs a multitude of mechanisms to subvert the immune system and successfully metastasize to distant organs. Concerningly, recent research also shows that tumor cells can disseminate early during melanoma progression and enter dormant states, eventually leading to metastases at a future time. Immune escape and metastasis have previously been viewed as separate phenomena; however, accumulating evidence is breaking down this dichotomy. Recent research into the progressive mechanisms of melanoma provides evidence that dedifferentiation similar to classical epithelial to mesenchymal transition (EMT), genes involved in neural crest stem cell maintenance, and hypoxia/acidosis, are important factors simultaneously involved in immune escape and metastasis. The likeness between EMT and early dissemination, and differences, also become apparent in these contexts. Detailed knowledge of the mechanisms behind “dual drivers” simultaneously promoting metastatically inclined and immunosuppressive environments can yield novel strategies effective in disabling multiple facets of melanoma progression. Furthermore, understanding progression through these drivers may provide insight towards novel treatments capable of preventing recurrence arising from dormant dissemination or improving immunotherapy outcomes.

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“…For example, in human ovarian cancer, tumor-associated MSCs (T-MSCs) were discovered to produce more bone morphogenetic proteins (BMPs) compared with normal MSCs (N-MSCs) derived from AT and BM, including BMP2, BMP4, and BMP6 69 . Studies indicated that BMP2/4 can promote the progression of various types of cancers, such as prostate 70 , melanoma 71 , and breast cancer 72 . Koushan et al isolated MSCs from stage II breast tumor samples that had undergone chemotherapy or radiotherapy.…”

Section: Polarization Of Mscs and Its Dual Role In Breast Cancer Prog...mentioning

confidence: 99%

The Role of Mesenchymal Stem Cells in Modulating the Breast Cancer Microenvironment

Zhang

2023

Cell Transplant

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The role of mesenchymal stem cells (MSCs) in the breast tumor microenvironment (TME) is significant and multifaceted. MSCs are recruited to breast tumor sites through molecular signals released by tumor sites. Once in the TME, MSCs undergo polarization and interact with various cell populations, including immune cells, cancer-associated fibroblasts (CAFs), cancer stem cells (CSCs), and breast cancer cells. In most cases, MSCs play roles in breast cancer therapeutic resistance, but there is also evidence that indicates their abilities to sensitize cancer cells to chemotherapy and radiotherapy. MSCs possess inherent regenerative and homing properties, making them attractive candidates for cell-based therapies. Therefore, MSCs can be engineered to express therapeutic molecules or deliver anti-cancer agents directly to tumor sites. Unraveling the intricate relationship between MSCs and the breast TME has the potential to uncover novel therapeutic targets and advance our understanding of breast cancer biology.

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BMP Signaling Promotes Neural Crest Identity and Accelerates Melanoma Onset

Cited by 7 publications

References 14 publications

Construction and Validation of a Ferroptosis-Related Prognostic Signature for Melanoma Based on Single-Cell RNA Sequencing

Construction and Validation of a Ferroptosis-Related Prognostic Signature for Melanoma Based on Single-Cell RNA Sequencing

Immune escape and metastasis mechanisms in melanoma: breaking down the dichotomy

The Role of Mesenchymal Stem Cells in Modulating the Breast Cancer Microenvironment

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