EMP2 acts as a suppressor of melanoma and is negatively regulated by mTOR-mediated autophagy

Wang, Manyi; Li, Sijia; Zhang, Peng; Wang, Yujia; Wang, Chunting; Bai, Ding; Jiang, Xian

doi:10.7150/jca.30342

Cited by 7 publications

(8 citation statements)

References 43 publications

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“…EMP3 is induced by TWIST1/2 and regulates epithelial-to-mesenchymal transition of gastric cancer cells [30]. In line with the role of EMP2 in nasopharyngeal cancer and melanoma [31,32], EMP2 overexpression inhibited cell proliferation, migration, and invasion and caused G1 cell cycle arrest, while downregulation of EMP2 by siRNA resulted in an enhanced cell migratory ability. We did not perform proliferation assay after EMP2 knockdown, since the downregulation of EMP2 by siRNA was transient and could be recovered after 3-4 days, while the observation time for the proliferation assay was 5-day long.…”

Section: Discussionmentioning

confidence: 72%

Epithelial Membrane Protein 2 Suppresses Non-Small Cell Lung Cancer Cell Growth by Inhibition of MAPK Pathway

Schröder

Nenkov

et al. 2021

IJMS

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Epithelial membrane proteins (EMP1-3) are involved in epithelial differentiation and carcinogenesis. Dysregulated expression of EMP2 was observed in various cancers, but its role in human lung cancer is not yet clarified. In this study, we analyzed the expression of EMP1-3 and investigated the biological function of EMP2 in non-small cell lung cancer (NSCLC). The results showed that lower expression of EMP1 was significantly correlated with tumor size in primary lung tumors (p = 0.004). Overexpression of EMP2 suppressed tumor cell growth, migration, and invasion, resulting in a G1 cell cycle arrest, with knockdown of EMP2 leading to enhanced cell migration, related to MAPK pathway alterations and disruption of cell cycle regulatory genes. Exosomes isolated from transfected cells were taken up by tumor cells, carrying EMP2-downregulated microRNAs (miRNAs) which participated in regulation of the tumor microenvironment. Our data suggest that decreased EMP1 expression is significantly related to increased tumor size in NSCLC. EMP2 suppresses NSCLC cell growth mainly by inhibiting the MAPK pathway. EMP2 might further affect the tumor microenvironment by regulating tumor microenvironment-associated miRNAs.

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Section: Discussionmentioning

confidence: 72%

Epithelial Membrane Protein 2 Suppresses Non-Small Cell Lung Cancer Cell Growth by Inhibition of MAPK Pathway

Schröder

Nenkov

et al. 2021

IJMS

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“…Surgical resection is the main therapeutic approach for patients with early melanoma. Given the high malignancy degree of patients with melanoma in advanced stages, the effect of standardized treatment is poor, and the accompanying diagnosis and individualized targeted therapy have become important strategies [1][2][3][4][5][6][7][8]. Several kinase inhibitors, including BRAF inhibitor vemurafenib and dabrafenib, MEK1/2 inhibitor trametinib, c-kit inhibitor imatinib and nilotinib, and other inhibitors targeted to the PI3K/Akt/mTOR signaling pathways, have been approved for the treatment of metastatic melanoma [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Novel HSP90-PI3K Dual Inhibitor Suppresses Melanoma Cell Proliferation by Interfering with HSP90-EGFR Interaction and Downstream Signaling Pathways

Zhao

Zhu

Xie

et al. 2020

IJMS

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Melanoma is the deadliest form of skin cancer, and its incidence has continuously increased over the past 20 years. Therefore, the discovery of a novel targeted therapeutic strategy for melanoma is urgently needed. In our study, MTT-based cell proliferation assay, cell cycle, and apoptosis assays through flow cytometry, protein immunoblotting, protein immunoprecipitation, designing of melanoma xenograft models, and immunohistochemical/immunofluorescent assays were carried out to determine the detailed molecular mechanisms of a novel HSP90-PI3K dual inhibitor. Our compound, named DHP1808, was found to suppress A375 cell proliferation through apoptosis induction by activating the Fas/FasL signaling pathway; it also induced cell-cycle arrest and inhibited the cell migration and invasion of A375 cells by interfering with Hsp90-EGFR interactions and downstream signaling pathways. Our results indicate that DHP1808 could be a promising lead compound for the Hsp90/PI3K dual inhibitor.

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“…mTOR plays a pivotal role in the control of cell growth and proliferation and is an important target of anticancer drugs [36]. mTORinh have shown some efficacy in melanoma [37]; however, the role of mTORinh on melanoma progression still remains unclear [38].…”

Section: Discussionmentioning

confidence: 99%

Outcome of pretransplant melanoma after solid organ transplantation: an observational study

et al. 2021

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Summary The number of patients with a history of melanoma who are awaiting a solid organ transplantation (SOT) is increasing. Few recommendations exist on the timing to transplantation after melanoma diagnosis. The aim of this study was to assess the melanoma recurrence‐free survival after pretransplant melanoma (PTM). We conducted a multicenter ambispective observational study. Organ transplant recipients (OTR) with a history of PTM and complete AJCC staging were included. Thirty‐seven patients (predominantly men with a renal allograft) were included. Five melanomas were in situ, 21 stage IA, 4 stage IB, 5 stage II, and 2 stage IIIB. The median post‐transplantation follow‐up time was 4 years. Sixty‐two percent of patients were followed up more than 2 years. Recurrence‐free survival since melanoma reached 89.9%, but varied significantly according to AJCC staging (P = 0.0129). Three patients presented a recurrence. Despite the rather limited sample size and a wide range of follow‐up, our findings concerning the recurrence‐free survival appear reassuring for in situ and stage IA PTM; accordingly, we suggest that a waiting time to transplantation is not mandatory in patients with in situ or stage IA PTM, especially whenever SOT is urgently needed. Caution is, however, needed for patients with higher stage.

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EMP2 acts as a suppressor of melanoma and is negatively regulated by mTOR-mediated autophagy

Cited by 7 publications

References 43 publications

Epithelial Membrane Protein 2 Suppresses Non-Small Cell Lung Cancer Cell Growth by Inhibition of MAPK Pathway

Epithelial Membrane Protein 2 Suppresses Non-Small Cell Lung Cancer Cell Growth by Inhibition of MAPK Pathway

Novel HSP90-PI3K Dual Inhibitor Suppresses Melanoma Cell Proliferation by Interfering with HSP90-EGFR Interaction and Downstream Signaling Pathways

Outcome of pretransplant melanoma after solid organ transplantation: an observational study

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