Evidence map›Paper›PMID 40545870›Full record

ArticleCancer2025

Mitochondrial proteome landscape unveils key insights into melanoma severity and treatment strategies.

Yonghyo Kim, Viktória Doma, Uğur Çakır, Magdalena Kuras, Lazaro Hiram Betancourt, Indira Pla, Aniel Sanchez, Yutaka Sugihara, Roger Appelqvist, Henriett Oskolas and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors.

Yonghyo KimDivision of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Viktória DomaDepartment of Dermatology, Venereology and Dermatooncology, Semmelweis University, Budapest, Hungary.
Uğur ÇakırDepartment of Dermatology, Venereology and Dermatooncology, Semmelweis University, Budapest, Hungary.
Magdalena KurasSection for Clinical Chemistry, Department of Translational Medicine, Lund University, Lund, Sweden.
Lazaro Hiram BetancourtSection for Clinical Chemistry, Department of Translational Medicine, Lund University, Lund, Sweden.
Indira PlaSection for Clinical Chemistry, Department of Translational Medicine, Lund University, Lund, Sweden.
Aniel SanchezSection for Clinical Chemistry, Department of Translational Medicine, Lund University, Lund, Sweden.
Yutaka SugiharaDivision of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Roger AppelqvistDepartment of Biomedical Engineering, Clinical Protein Science & Imaging, Lund University, Lund, Sweden.ORCID https://orcid.org/0000-0001-7450-7216
Henriett OskolasSection for Clinical Chemistry, Department of Translational Medicine, Lund University, Lund, Sweden.
Boram LeeDivision of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Jéssica GuedesSection for Clinical Chemistry, Department of Translational Medicine, Lund University, Lund, Sweden.
Gustavo MonneratDepartamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Gabriel Reis Alves CarneiroDepartamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Fábio C S NogueiraDepartamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Gilberto B DomontDepartamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Johan MalmSection for Clinical Chemistry, Department of Translational Medicine, Lund University, Lund, Sweden.
Bo BaldetorpDivision of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Elisabet WieslanderSection for Clinical Chemistry, Department of Translational Medicine, Lund University, Lund, Sweden.
István Balázs NémethDepartment of Dermatology and Allergology, University of Szeged, Szeged, Hungary.
A Marcell SzászDepartment of Bioinformatics, Semmelweis University, Budapest, Hungary.
Runyu HongDepartment of Biochemistry and Pharmacology, Institute for systems genetics, New York University, Grossman School of Medicine, New York, New York, USA.
Krzysztof PawłowskiSection for Clinical Chemistry, Department of Translational Medicine, Lund University, Lund, Sweden.
Melinda RezeliDepartment of Biomedical Engineering, Clinical Protein Science & Imaging, Lund University, Lund, Sweden.
Ho Jeong KwonDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Jozsef TimarDepartment of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary.
David FenyöDepartment of Biochemistry and Pharmacology, Institute for systems genetics, New York University, Grossman School of Medicine, New York, New York, USA.
Sarolta KárpátiDepartment of Dermatology, Venereology and Dermatooncology, Semmelweis University, Budapest, Hungary.
György Marko-VargaDepartment of Biomedical Engineering, Clinical Protein Science & Imaging, Lund University, Lund, Sweden.
Jeovanis GilSection for Clinical Chemistry, Department of Translational Medicine, Lund University, Lund, Sweden.ORCID https://orcid.org/0000-0003-3601-3893

Funding

Crafoordska Stiftelsen 20240554Fru Berta Kamprads StiftelseNational Research Foundation of Korea 2015K1A1A2028365National Research Foundation of Korea 2016K2A9A1A03904900National Research Foundation of Korea 2021R1A3B1077371
6 · The paper itself

Abstract

backgroundMelanoma, 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.

methodsQuantitative 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.

resultsMitochondrial 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.

conclusionsThis 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.

Indexed as

MelanomaMitochondriaMitochondrial ProteinsProteomeSkin NeoplasmsApoptosisCell Line, TumorCell ProliferationDrug Resistance, NeoplasmFemaleHumansMaleMiddle AgedOxidative PhosphorylationProspective StudiesProteomicsBRAF protein, humanMitochondrial ProteinsProteomeProto-Oncogene Proteins B-rafBRAF mutationMCM complexmelanomamitochondrial metabolismmitochondrial proteomemitoribosomesoxidative phosphorylationproteomics

Identifiers

PMID40545870
PMCPMC12183497

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.