Wenqiong Ma: Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Zexiu Wu: Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Mazaher Maghsoudloo: Faculty of Advanced Science and Technology, Department of Genetics, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Iqra Ijaz: Sichuan Provincial Center for Gynecological and Breast Diseases, Southwest Medical University, Luzhou, Sichuan, China.
Marzieh Dehghan Shasaltaneh: Faculty of Science, Department of Biology, University of Zanjan, Zanjan, Iran.
Yuqin Zhang: Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Qiao Weng: Department of Obstetrics & Gynecology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Junjiang Fu: Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan, China.
Saber Imani: Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. ORCID
Qing Lian Wen: Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
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.
References
Science. 2012 Dec 21;338(6114):1622-6
[PMID: 23258894]
