Epithelial‐to‐mesenchymal‐like transition events in melanoma

Pedri, Dennis; Karras, Panagiotis; Landeloos, Ewout; Marine, Jean–Christophe; Rambow, Florian

doi:10.1111/febs.16021

Cited by 74 publications

(74 citation statements)

References 183 publications

(274 reference statements)

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“…In our study, Cx37 was increasingly expressed in samples of retinoblastoma, especially in the choroid and in the tumor tissue in comparison with the analyzed developing eyes. Increased Cx37 expression in the developing retina of the oldest prenatal eye might be in line with the preparation of the retina for the process of vascularization that occurs in the early postnatal period, which is also in line with our results that suggest a major decrease in expression of Cx37 in adulthood [ 26 ]. This could implicate aberrant Cx37 expression in the disruption of the early angiogenesis in humans, which was shown in previous studies conducted on Cx 37 −/− mouse models.…”

Section: Discussionsupporting

confidence: 90%

“…This finding might be correlated by increased epithelial to mesenchymal transition (EMT) that is observed in this type of melanoma. Namely, EMT epithelial tumor cells acquire properties of mesenchymal cells, which might contribute to metastatic dissemination and cancer therapy resistance [ 26 ]. Increased Cx37 that we observed in our study might be connected to the spreading of the new capillary network in tumor tissue that additionally supports the tumor’s ability for metastasis spreading and a decrease in its sensitivity to therapy.…”

Section: Discussionmentioning

confidence: 99%

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The Expression of Connexin 37, 40, 43, 45 and Pannexin 1 in the Early Human Retina and Choroid Development and Tumorigenesis

Žužul

Lozić

Filipović

et al. 2022

IJMS

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The expression pattern of Connexins (Cx) 37, 40, 43, 45 and Pannexin 1 (Pnx1) was analyzed immunohistochemically, as well as semi-quantitatively and quantitatively in histological sections of developing 8th- to 12th-week human eyes and postnatal healthy eye, in retinoblastoma and different uveal melanomas. Expressions of both Cx37 and Cx43 increased during development but diminished in the postnatal period, being higher in the retina than in the choroid. Cx37 was highly expressed in the choroid of retinoblastoma, and Cx43 in epitheloid melanoma, while they were both increasingly expressed in mixoid melanoma. In contrast, mild retinal Cx40 expression during development increased to strong in postnatal period, while it was significantly higher in the choroid of mixoid melanoma. Cx45 showed significantly higher expression in the developing retina compared to other samples, while it became low postnatally and in all types of melanoma. Pnx1 was increasingly expressed in developing choroid but became lower in the postnatal eye. It was strongly expressed in epithelial and spindle melanoma, and particularly in retinoblastoma. Our results indicate importance of Cx37 and Cx40 expression in normal and pathological vascularization, and Cx43 expression in inflammatory response. Whereas Cx45 is involved in early stages of eye development, Pnx1might influence cell metabolism. Additionally, Cx43 might be a potential biomarker of tumor prognosis.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

The Expression of Connexin 37, 40, 43, 45 and Pannexin 1 in the Early Human Retina and Choroid Development and Tumorigenesis

Žužul

Lozić

Filipović

et al. 2022

IJMS

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“…EMT is important in carcinogenesis and metastasis [ 29 ]. Growing evidence shows that non-epithelial tumors, including MM, also have mesenchymal-like characteristics, which help the tumor cells to acquire strong metastatic ability [ 30 ]. Therefore, we speculate that Ebp1 may enhance MM cells invasion and metastasis by inducing EMT.…”

Section: Discussionmentioning

confidence: 99%

ERBB3 binding protein 1 promotes the progression of malignant melanoma through activation of the Wnt/ β-catenin signaling pathway

et al. 2022

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Background Malignant melanoma (MM) is highly metastatic and has the highest mortality rate in patients with skin cancer. The ERBB3 binding protein 1 (Ebp1) has been linked to the onset and progression of a number of malignancies. However, the role of Ebp1 in MM has not yet been reported. Methods Multiple databases were analyzed for comparing the expression of Ebp1 in normal skin and MM. Ebp1 expression was knocked down in A375 and B16 cells, and the impact of Ebp1 on the cell growth was tested by CCK-8, plate clone colony, and cell cycle assays. Scratch, transwell, and in vivo caudal vein lung metastasis tests were also used to confirm the effects of Ebp1 on melanoma cells migration, invasion, and metastasis. Furthermore, the possible molecular mechanism of Ebp1 was predicted by set enrichment analysis and verified by western blotting. Results Ebp1 expression was substantially higher in MM than it was in normal skin, and Ebp1 was linked to the clinical stage and lymph node metastases of patients with MM. Knockdown of Ebp1 inhibited cell proliferation, migration, and invasion. In vivo experiments further verified that the knockdown of Ebp1 had an obvious inhibitory effect on lung metastasis in nude mice. Knockdown of Ebp1 reduced vimentin, N-cadherin, slug, and snail expression while increasing E-cadherin expression. Furthermore, knockdown of Ebp1 reduced the expression of β-catenin, as well as its downstream targets CyclinD1 and p-GSK3β; however, a Wnt/β-catenin agonist could reverse this effect. Conclusion Ebp1 may promote the proliferation and metastasis of melanoma cells through activation of the Wnt/β-catenin pathway. Graphical Abstract

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“…It is tempting to speculate that this hybrid phenotype and "mesenchymal heritage" of melanocytes is related to their propensity to form benign metastasis as discussed above. Nonetheless, "EMT-like" dedifferentiation of melanoma cells has been shown to contribute to tumor cell invasion, much like EMT in carcinomas [59]. In addition, melanoma collective migration and LVI was shown to be regulated by tumor cell expression of the cell surface protease MMP16, which cleaved and de-activated molecules involved in single cell migration and blood vessel invasion [60].…”

Section: Local Invasionmentioning

confidence: 99%

Mechanisms and Clinical Significance of Tumor Lymphatic Invasion

Fujimoto

2021

Cells

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Tumor-associated lymphatic vessels play an important role in tumor progression, mediating lymphatic dissemination of malignant cells to tumor-draining lymph nodes and regulating tumor immunity. An early, necessary step in the lymphatic metastasis cascade is the invasion of lymphatic vessels by tumor cell clusters or single tumor cells. In this review, we discuss our current understanding of the underlying cellular and molecular mechanisms, which include tumor-specific as well as normal, developmental and immunological processes “hijacked” by tumor cells to gain access to the lymphatic system. Furthermore, we summarize the prognostic value of lymphatic invasion, discuss its relationship with local recurrence, lymph node and distant metastasis, and highlight potential therapeutic options and challenges.

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Epithelial‐to‐mesenchymal‐like transition events in melanoma

Cited by 74 publications

References 183 publications

The Expression of Connexin 37, 40, 43, 45 and Pannexin 1 in the Early Human Retina and Choroid Development and Tumorigenesis

The Expression of Connexin 37, 40, 43, 45 and Pannexin 1 in the Early Human Retina and Choroid Development and Tumorigenesis

ERBB3 binding protein 1 promotes the progression of malignant melanoma through activation of the Wnt/ β-catenin signaling pathway

Mechanisms and Clinical Significance of Tumor Lymphatic Invasion

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