Global Interactome Mapping Reveals Protumorigenic Interactions of NF-κB in Breast Cancer
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| Year of publication | 2025 |
| Type | Conference abstract |
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| Citation | |
| Description | NF-?B pathway is involved in inflammation; however, recent data shows its role also in cancer development and progression, including metastasis. To understand the role of NF-?B interactome dynamics in cancer, in this work (1) we study the complexity of breast cancer interactome in luminal A breast cancer model and its rearrangement associated with NF-?B modulation. Liquid chromatography-mass spectrometry measurement of 160 size-exclusion chromatography fractions identifies 5460 protein groups. Seven thousand five hundred sixty eight interactions among these proteins have been reconstructed by PrInCE algorithm, of which 2564 have been validated in independent datasets. NF-?B modulation leads to rearrangement of protein complexes involved in NF-?B signaling and immune response, cell cycle regulation, and DNA replication. Central NF-?B transcription regulator RELA co-elutes with interactors of NF-?B activator PRMT5, and these complexes are confirmed by AlphaPulldown prediction. A complementary immunoprecipitation experiment recapitulates RELA interactions with other NF-?B factors, associating NF-?B inhibition with lower binding of NF-?B activators to RELA. This study describes a network of protumorigenic protein interactions and their rearrangement upon NF-?B inhibition with potential therapeutic implications in tumors with high NF- ?B activity. This work was supported by the project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102) - Funded by the European Union - Next Generation EU. (1) Lapcik, Petr, R- Greg Stacey, David Potesil, Petr Kulhanek, Leonard J. Foster, Pavel Bouchal, Global Interactome Mapping Reveals Pro-tumorigenic Interactions of NF-?B in Breast Cancer. Molecular & Cellular Proteomics 2024, 23, 4, 100744. |
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