Mitochondrial proteome landscape unveils key insights into melanoma severity and treatment strategies
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| Název: | Mitochondrial proteome landscape unveils key insights into melanoma severity and treatment strategies |
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| Autoři: | Kim, Yonghyo, Doma, Viktória, Çakır, Uğur, Kuras, Magdalena, Betancourt, Lazaro Hiram, Pla, Indira, Sanchez, Aniel, Sugihara, Yutaka, Appelqvist, Roger, Oskolas, Henriett, Lee, Boram, Guedes, Jéssica, Monnerat, Gustavo, Carneiro, Gabriel Reis Alves, Nogueira, Fábio C S, Domont, Gilberto B, Malm, Johan, Baldetorp, Bo, Wieslander, Elisabet, Németh, István Balázs, Szász, A Marcell, Hong, Runyu, Pawłowski, Krzysztof, Rezeli, Melinda, Kwon, Ho Jeong, Timar, Jozsef, Fenyö, David, Kárpáti, Sarolta, Marko-Varga, György, Gil, Jeovanis |
| Přispěvatelé: | Lund University, Faculty of Medicine, Department of Translational Medicine, Clinical Chemistry, Malmö, Lunds universitet, Medicinska fakulteten, Institutionen för translationell medicin, Klinisk kemi, Malmö, Originator, Lund University, Profile areas and other strong research environments, Other Strong Research Environments, LUCC: Lund University Cancer Centre, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Övriga starka forskningsmiljöer, LUCC: Lunds universitets cancercentrum, Originator, Lund University, Faculty of Engineering, LTH, Departments at LTH, Department of Biomedical Engineering, Division for Biomedical Engineering, Lunds universitet, Lunds Tekniska Högskola, Institutioner vid LTH, Institutionen för biomedicinsk teknik, Avdelningen för biomedicinsk teknik, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section V, Mass Spectrometry, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion V, Masspektrometri, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section V, Mass Spectrometry, Clinical Protein Science and Imaging, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion V, Masspektrometri, Clinical Protein Science and Imaging, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Biomarkers and epidemiology, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Biomarkörer och Epi, Originator, Lund University, Profile areas and other strong research environments, Strategic research areas (SRA), EpiHealth: Epidemiology for Health, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Strategiska forskningsområden (SFO), EpiHealth: Epidemiology for Health, Originator, Lund University, Faculty of Medicine, Department of Translational Medicine, Lunds universitet, Medicinska fakulteten, Institutionen för translationell medicin, Originator, Lund University, Profile areas and other strong research environments, Lund University Profile areas, LU Profile Area: Light and Materials, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Lunds universitets profilområden, LU profilområde: Ljus och material, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section V, Mass Spectrometry, BioMS, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion V, Masspektrometri, BioMS, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Medical oncology, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Medicinsk onkologi, Originator |
| Zdroj: | Cancer. 131(13) |
| Témata: | Medical and Health Sciences, Basic Medicine, Basic Cancer Research, Medicin och hälsovetenskap, Medicinska och farmaceutiska grundvetenskaper, Basal cancerforskning, Clinical Medicine, Cancer and Oncology, Klinisk medicin, Cancer och onkologi |
| Popis: | BACKGROUND: Melanoma, the deadliest form of skin cancer, exhibits resistance to conventional therapies, particularly in advanced and metastatic stages. Mitochondrial pathways, including oxidative phosphorylation and mitochondrial translation, have emerged as critical drivers of melanoma progression and therapy resistance. This study investigates the mitochondrial proteome in melanoma to uncover novel therapeutic vulnerabilities. METHODS: Quantitative proteomics was performed on 151 melanoma-related samples from a prospective cohort and postmortem tissues. Differential expression analysis identified mitochondrial proteins linked to disease aggression and treatment resistance. Functional enrichment analyses and in vitro validation using mitochondrial inhibitors were conducted to evaluate therapeutic potential. RESULTS: Mitochondrial translation and oxidative phosphorylation (OXPHOS) were significantly upregulated in aggressive melanomas, particularly in BRAF-mutant and metastatic tumors. Inhibition of mitochondrial pathways using antibiotics (doxycycline, tigecycline, and azithromycin) and OXPHOS inhibitors (VLX600, IACS-010759, and BAY 87-2243) demonstrated dose-dependent antiproliferative effects in melanoma cell lines, sparing noncancerous melanocytes. These treatments disrupted mitochondrial function, suppressed key metabolic pathways, and induced apoptosis, highlighting the clinical relevance of targeting these pathways. CONCLUSIONS: This study reveals mitochondrial pathways as critical drivers of melanoma progression and resistance, providing a rationale for targeting mitochondrial translation and OXPHOS in advanced melanoma. Combining mitochondrial inhibitors with existing therapies could overcome treatment resistance and improve patient outcomes. |
| Přístupová URL adresa: | https://doi.org/10.1002/cncr.35897 |
| Databáze: | SwePub |
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