Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways.
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 mela...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0285806&type=printable |
| _version_ | 1797238428944826368 |
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| author | Wenqiong Ma Zexiu Wu Mazaher Maghsoudloo Iqra Ijaz Marzieh Dehghan Shasaltaneh Yuqin Zhang Qiao Weng Junjiang Fu Saber Imani Qing Lian Wen |
| author_facet | Wenqiong Ma Zexiu Wu Mazaher Maghsoudloo Iqra Ijaz Marzieh Dehghan Shasaltaneh Yuqin Zhang Qiao Weng Junjiang Fu Saber Imani Qing Lian Wen |
| author_sort | Wenqiong Ma |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T17:35:30Z |
| format | Article |
| id | doaj.art-d9acfd359c354bb6a50f3ac9a9087ab1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-24T17:35:30Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d9acfd359c354bb6a50f3ac9a9087ab12024-03-28T05:35:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01187e028580610.1371/journal.pone.0285806Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways.Wenqiong MaZexiu WuMazaher MaghsoudlooIqra IjazMarzieh Dehghan ShasaltanehYuqin ZhangQiao WengJunjiang FuSaber ImaniQing Lian WenTo 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0285806&type=printable |
| spellingShingle | Wenqiong Ma Zexiu Wu Mazaher Maghsoudloo Iqra Ijaz Marzieh Dehghan Shasaltaneh Yuqin Zhang Qiao Weng Junjiang Fu Saber Imani Qing Lian Wen Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways. PLoS ONE |
| title | Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways. |
| title_full | Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways. |
| title_fullStr | Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways. |
| title_full_unstemmed | Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways. |
| title_short | Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways. |
| title_sort | dermokine mutations contribute to epithelial mesenchymal transition and advanced melanoma through erk mapk pathways |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0285806&type=printable |
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