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Proteomics discovery of MTDH and SND1 interaction vulnerabilities in ovarian cancer

Esmaeili, Parisa LU orcid ; Nasimian, Ahmad LU ; Werner, Lucas LU ; Junior, Sergio Mosquim LU orcid ; Jakobsson, Magnus E LU ; Gerdtsson, Anna Sandström LU ; Kazi, Julhash U LU orcid and Levander, Fredrik LU orcid (2025) In Scientific Reports 15(1).
Abstract

High-grade serous ovarian cancer (HGSOC) is the most prevalent and aggressive subtype of ovarian cancer. The combination of late-stage diagnosis and the tendency to exhibit resistance to existing treatments highlights a critical gap in effective therapeutic options. There is thus a need for novel strategies for targeting HGSOC, particularly in its advanced stages. To address this gap, we developed a comprehensive atlas profiling both the proteome and phosphoproteome levels across a panel of nine ovarian cancer cell lines from different subtypes. Subsequent differential expression analysis between the KURAMOCHI and the other cell lines, followed by phosphosite analyses, proposed the MTDH protein as a potential target. Further functional... (More)

High-grade serous ovarian cancer (HGSOC) is the most prevalent and aggressive subtype of ovarian cancer. The combination of late-stage diagnosis and the tendency to exhibit resistance to existing treatments highlights a critical gap in effective therapeutic options. There is thus a need for novel strategies for targeting HGSOC, particularly in its advanced stages. To address this gap, we developed a comprehensive atlas profiling both the proteome and phosphoproteome levels across a panel of nine ovarian cancer cell lines from different subtypes. Subsequent differential expression analysis between the KURAMOCHI and the other cell lines, followed by phosphosite analyses, proposed the MTDH protein as a potential target. Further functional analyses of MTDH and the interacting protein SND1 with RNA silencing, as well as targeting their interaction, revealed that disrupting this interaction leads to the dysregulation of several pathways associated with cancer progression and invasion. In particular, interference with the MTDH-SND1 complex was associated with enrichment of ferroptosis-related pathways. Moreover, combining C26A6 treatment with ferroptosis inducers produced enhanced inhibitory effects in ovarian cancer cells, suggesting a possible strategy for targeting cancer cell vulnerabilities in HGSOC, which warrants further investigation beyond in vitro models.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Female, Ovarian Neoplasms/metabolism, RNA-Binding Proteins, Membrane Proteins/metabolism, Proteomics/methods, Cell Line, Tumor, Cell Adhesion Molecules/metabolism, Gene Expression Regulation, Neoplastic, Nuclear Proteins/metabolism, Proteome, Endonucleases
in
Scientific Reports
volume
15
issue
1
article number
41818
publisher
Nature Publishing Group
external identifiers
  • scopus:105022795058
  • pmid:41286067
ISSN
2045-2322
DOI
10.1038/s41598-025-26913-1
language
English
LU publication?
yes
additional info
© 2025. The Author(s).
id
c2e4a69b-709d-48c4-9937-bc814920638a
date added to LUP
2025-12-26 22:01:08
date last changed
2026-01-10 05:29:00
@article{c2e4a69b-709d-48c4-9937-bc814920638a,
  abstract     = {{<p>High-grade serous ovarian cancer (HGSOC) is the most prevalent and aggressive subtype of ovarian cancer. The combination of late-stage diagnosis and the tendency to exhibit resistance to existing treatments highlights a critical gap in effective therapeutic options. There is thus a need for novel strategies for targeting HGSOC, particularly in its advanced stages. To address this gap, we developed a comprehensive atlas profiling both the proteome and phosphoproteome levels across a panel of nine ovarian cancer cell lines from different subtypes. Subsequent differential expression analysis between the KURAMOCHI and the other cell lines, followed by phosphosite analyses, proposed the MTDH protein as a potential target. Further functional analyses of MTDH and the interacting protein SND1 with RNA silencing, as well as targeting their interaction, revealed that disrupting this interaction leads to the dysregulation of several pathways associated with cancer progression and invasion. In particular, interference with the MTDH-SND1 complex was associated with enrichment of ferroptosis-related pathways. Moreover, combining C26A6 treatment with ferroptosis inducers produced enhanced inhibitory effects in ovarian cancer cells, suggesting a possible strategy for targeting cancer cell vulnerabilities in HGSOC, which warrants further investigation beyond in vitro models.</p>}},
  author       = {{Esmaeili, Parisa and Nasimian, Ahmad and Werner, Lucas and Junior, Sergio Mosquim and Jakobsson, Magnus E and Gerdtsson, Anna Sandström and Kazi, Julhash U and Levander, Fredrik}},
  issn         = {{2045-2322}},
  keywords     = {{Humans; Female; Ovarian Neoplasms/metabolism; RNA-Binding Proteins; Membrane Proteins/metabolism; Proteomics/methods; Cell Line, Tumor; Cell Adhesion Molecules/metabolism; Gene Expression Regulation, Neoplastic; Nuclear Proteins/metabolism; Proteome; Endonucleases}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Proteomics discovery of MTDH and SND1 interaction vulnerabilities in ovarian cancer}},
  url          = {{http://dx.doi.org/10.1038/s41598-025-26913-1}},
  doi          = {{10.1038/s41598-025-26913-1}},
  volume       = {{15}},
  year         = {{2025}},
}