The Complex Role of Autophagy in Melanoma Evolution: New Perspectives From Mouse Models

Leo, Luca Di; Bodemeyer, Valérie; Zio, Daniela De

doi:10.3389/fonc.2019.01506

Cited by 18 publications

(12 citation statements)

References 96 publications

(150 reference statements)

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“…Autophagy was suggested to have a role during melanoma development and progression 47 , 48 . However, we were not able to correlate either the pro-invasive state of BPA −/− melanoma or the hyperactivation of FAK1 signaling to the AMBRA1 pro-autophagy functions 7 .…”

Section: Discussionmentioning

confidence: 99%

Loss of Ambra1 promotes melanoma growth and invasion

et al. 2021

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Melanoma is the deadliest skin cancer. Despite improvements in the understanding of the molecular mechanisms underlying melanoma biology and in defining new curative strategies, the therapeutic needs for this disease have not yet been fulfilled. Herein, we provide evidence that the Activating Molecule in Beclin-1-Regulated Autophagy (Ambra1) contributes to melanoma development. Indeed, we show that Ambra1 deficiency confers accelerated tumor growth and decreased overall survival in Braf/Pten-mutated mouse models of melanoma. Also, we demonstrate that Ambra1 deletion promotes melanoma aggressiveness and metastasis by increasing cell motility/invasion and activating an EMT-like process. Moreover, we show that Ambra1 deficiency in melanoma impacts extracellular matrix remodeling and induces hyperactivation of the focal adhesion kinase 1 (FAK1) signaling, whose inhibition is able to reduce cell invasion and melanoma growth. Overall, our findings identify a function for AMBRA1 as tumor suppressor in melanoma, proposing FAK1 inhibition as a therapeutic strategy for AMBRA1 low-expressing melanoma.

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Section: Discussionmentioning

confidence: 99%

Loss of Ambra1 promotes melanoma growth and invasion

et al. 2021

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“…Mitochondrial autophagy has been reported to play a vital role in human diseases, including cancer (37). However, the relationship between autophagy and cancer is still obscure (38,39). The role of autophagy in cancer may depend on the environment and the stage of tumorigenesis (40).…”

Section: Discussionmentioning

confidence: 99%

Mefloquine Inhibits Esophageal Squamous Cell Carcinoma Tumor Growth by Inducing Mitochondrial Autophagy

Xie

Zhang

et al. 2020

Front. Oncol.

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Esophageal squamous cell carcinoma (ESCC) has a worldwide impact on human health, due to its high incidence and mortality. Therefore, identifying compounds to increase patients' survival rate is urgently needed. Mefloquine (MQ) is an FDA-approved anti-malarial drug, which has been reported to inhibit cellular proliferation in several cancers. However, the anti-tumor activities of the drug have not yet been completely defined. In this study, mass spectrometry was employed to profile proteome changes in ESCC cells after MQ treatment. Sub-cellular localization and gene ontology term enrichment analysis suggested that MQ treatment mainly affect mitochondria. The KEGG pathway enrichment map of down-regulated pathways and Venn diagram indicated that all of the top five down regulated signaling pathways contain four key mitochondrial proteins (succinate dehydrogenase complex subunit C (SDHC), succinate dehydrogenase complex subunit D, mitochondrially encoded cytochrome c oxidase III and NADH: ubiquinone oxidoreductase subunit V3). Meanwhile, mitochondrial autophagy was observed in MQ-treated KYSE150 cells. More importantly, patient-derived xenograft mouse models of ESCC with SDHC high expression were more sensitive to MQ treatment than low SDHC-expressing xenografts. Taken together, mefloquine inhibits ESCC tumor growth by inducing mitochondrial autophagy and SDHC plays a vital role in MQ-induced anti-tumor effect on ESCC.

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“…Interestingly, galectin-3, which belong to a superfamily of lectins, was found to decrease the level of autophagy in vemurafenib treated melanoma cells [ 49 ]. Because autophagy is recognized as a critical metabolic process involved in melanoma development and is associated with numerous molecular triggers [ 50 ], we looked further into the metallomics profiles in melanoma cells.…”

Section: Resultsmentioning

confidence: 99%

Tracking of Glycans Structure and Metallomics Profiles in BRAF Mutated Melanoma Cells Treated with Vemurafenib

Nisiewicz

Kowalczyk

Sobiepanek

et al. 2021

IJMS

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Nearly half of patients with advanced and metastatic melanomas harbor a BRAF mutation. Vemurafenib (VEM), a BRAF inhibitor, is used to treat such patients, however, responses to VEM are very short-lived due to intrinsic, adaptive and/or acquired resistance. In this context, we present the action of the B-Raf serine-threonine protein kinase inhibitor (vemurafenib) on the glycans structure and metallomics profiles in melanoma cells without (MeWo) and with (G-361) BRAF mutations. The studies were performed using α1-acid glycoprotein (AGP), a well-known acute-phase protein, and concanavalin A (Con A), which served as the model receptor. The detection of changes in the structure of glycans can be successfully carried out based on the frequency shifts and the charge transfer resistance after interaction of AGP with Con A in different VEM treatments using QCM-D and EIS measurements. These changes were also proved based on the cell ultrastructure examined by TEM and SEM. The LA-ICP-MS studies provided details on the metallomics profile in melanoma cells treated with and without VEM. The studies evidence that vemurafenib modifies the glycans structures and metallomics profile in melanoma cells harboring BRAF mutation that can be further implied in the resistance phenomenon. Therefore, our data opens a new avenue for further studies in the short-term addressing novel targets that hopefully can be used to improve the therapeutic regiment in advanced melanoma patients. The innovating potential of this study is fully credible and has a real impact on the global patient society suffering from advanced and metastatic melanomas.

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The Complex Role of Autophagy in Melanoma Evolution: New Perspectives From Mouse Models

Cited by 18 publications

References 96 publications

Loss of Ambra1 promotes melanoma growth and invasion

Loss of Ambra1 promotes melanoma growth and invasion

Mefloquine Inhibits Esophageal Squamous Cell Carcinoma Tumor Growth by Inducing Mitochondrial Autophagy

Tracking of Glycans Structure and Metallomics Profiles in BRAF Mutated Melanoma Cells Treated with Vemurafenib

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