Physical Interactions of Dmnk with Orb: Implications in the Regulated Localization of Orb by Dmnk during Oogenesis and Embryogenesis

Iwai, Kenji; Oishi, Isao; Xu, Xiao Zhou; Minami, Yasuhiro; Yamamura, Hirohei

doi:10.1006/bbrc.2001.6166

“…Recently, researchers have detected the different isoforms of DMNK-β in various cancer tissues. Various cancer cell types have differences in the expression and relevance of DMKN as either a tumor suppressor gene or an oncogene [18,[64][65][66]. The expression of DMNK-α and -γ is not observed in keratinocyte-derived tumor cells such as MM, keratosis, and basal cell cancer although DMNK-β expression in cultured human keratinocytes is associated with cell adhesion and inhibits cancer metastasis [7,14].…”

Section: Plos Onementioning

confidence: 99%

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

Ma

¹

,

Wu

²

,

Maghsoudloo

³

et al. 2023

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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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“…Recently, researchers have detected the different isoforms of DMNK-β in various cancer tissues. Various cancer cell types have differences in the expression and relevance of DMKN as either a tumor suppressor gene or an oncogene 18, [30][31][32] . The expression of DMNK-α and -γ is not observed in keratinocyte-derived tumor cells such as MM, keratosis, and basal cell cancer although DMNK-β expression in cultured human keratinocytes is associated with cell adhesion and inhibits cancer metastasis 7,14 .…”

Section: Discussionmentioning

confidence: 99%

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

Imani

¹

,

Ma

²

,

Wu

³

et al. 2023

Preprint

0

View full text Add to dashboard Cite

In the present study, the vulnerability associated with dermokine (DMKN), as a new trigger for the Epithelial-Mesenchymal Transition (EMT)-driven melanoma, was assessed based on a genome-wide genetic screening using transgenic. The results suggested a significantly higher DMKN expression in human Malignant Melanoma (MM), which was correlated with poor overall survival among melanoma patients, especially BRAF-mutated MM samples. Additionally, an in vitro knockdown of DMKN inhibited the cell proliferation, invasion, and apoptosis of MM cancer cells by activating ERK/MAPK signaling pathways and regulating STAT3 in downstream molecules. The interrogation of in vitro melanoma dataset and characterization of advanced melanoma samples revealed that DMKN downregulated the EMT-like transcriptional program through disrupting MET/EMT cortical actin, enhanced the expression of epithelial markers, and decreased that of mesenchymal markers. Whole-exome sequencing was presented with p.E69D and p.V91A DMKN mutations as novel somatic loss-of-function mutations. Further, the purposeful proof-of-principle modeled the interaction of ERK with p.E69D and p.V91A DMKN mutations in the ERK-MAPK kinase signaling that may be naturally associated with the EMT triggering during the melanomagenesis. These results provided preclinical evidence for the role of DMKN in shaping the EMT-like melanoma phenotype and introduced DMKN as a new exceptional responder to personalized MM therapy.

show abstract

“…Recently, researchers have detected the different isoforms of DMNK-β in various cancer tissues. Various cancer cell types have differences in the expression and relevance of DMKN as either a tumor suppressor gene or an oncogene [18, [30][31][32]. The expression of DMNK-α and -γ is not observed in keratinocytederived tumor cells such as MM, keratosis, and basal cell cancer although DMNK-β expression in cultured human keratinocytes is associated with cell adhesion and inhibits cancer metastasis [7,14].…”

Section: Discussionmentioning

confidence: 99%

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

Imani

¹

,

Ma

²

,

Wu

³

et al. 2022

Preprint

0

View full text Add to dashboard Cite

In the present study, the vulnerability associated with dermokine (DMKN), as a new trigger for the Epithelial-Mesenchymal Transition (EMT)-driven melanoma, was assessed based on a genome-wide genetic screening using transgenic. The results suggested a significantly higher DMKN expression in human Malignant Melanoma (MM), which was correlated with poor overall survival among melanoma patients, especially BRAF-mutated MM samples. Additionally, an in vitro knockdown of DMKN inhibited the cell proliferation, invasion, and apoptosis of MM cancer cells by activating ERK/MAPK signaling pathways and regulating STAT3 in downstream molecules. The interrogation of in vitro melanoma dataset and characterization of advanced melanoma samples revealed that DMKN downregulated the EMT-like transcriptional program through disrupting MET/EMT cortical actin, enhanced the expression of epithelial markers, and decreased that of mesenchymal markers. Whole-exome sequencing was presented with p.E69D and p.V91A DMKN mutations as novel somatic loss-of-function mutations. Further, the purposeful proof-of-principle modeled the interaction of ERK with p.E69D and p.V91A DMKN mutations in the ERK-MAPK kinase signaling that may be naturally associated with the EMT triggering during the melanomagenesis. These results provided preclinical evidence for the role of DMKN in shaping the EMT-like melanoma phenotype and introduced DMKN as a new exceptional responder to personalized MM therapy.

show abstract

Physical Interactions of Dmnk with Orb: Implications in the Regulated Localization of Orb by Dmnk during Oogenesis and Embryogenesis

Cited by 4 publications

References 28 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

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

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