Global Interactome Mapping Reveals Pro-tumorigenic Interactions
of NF-κB in Breast Cancer

a 2023

Global Interactome Mapping Reveals Pro-tumorigenic Interactions of NF-κB in Breast Cancer

LAPČÍK, Petr, Greg R. STACEY, David POTĚŠIL, Leonard J. FOSTER, Pavel BOUCHAL et. al.

Základní údaje

Originální název

Global Interactome Mapping Reveals Pro-tumorigenic Interactions of NF-κB in Breast Cancer

Název česky

Globální mapování interaktomu odhaluje pro-tumorigenické interakce NF-κB v nádorech prsu

Autoři

LAPČÍK, Petr (203 Česká republika, domácí), Greg R. STACEY (124 Kanada), David POTĚŠIL (203 Česká republika, domácí), Leonard J. FOSTER (124 Kanada) a Pavel BOUCHAL (203 Česká republika, garant, domácí)

Vydání

In Book of Abstracts of 22nd Human Proteome Organization World Congress, Busan, Korea 17.9.-21.9.2023, PP01.50, 2023

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Kód RIV

RIV/00216224:14310/23:00132137

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

proteomics; NF-κB; Protein complexes; Breast cancer; Protein correlation profiling

Příznaky

Mezinárodní význam

Změněno: 5. 4. 2024 11:33, Mgr. Marie Šípková, DiS.

Anotace

V originále

Introduction: NF-κB pathway plays a key role in immune response and inflammation, however, our previous results supported by data from other studies show its role also in cancer development and progression, including lymph node metastasis of luminal A breast cancer [1]. Here we used size exclusion chromatography (SEC) fractionation and protein correlation profiling (PCP) [2] to study the impact of NF-κB modulation on global protein interactome dynamics in luminal A breast cancer model. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of 160 SEC fractions of native MCF-7 lysates with inhibited or innate NF-κB activity was performed and the PrInCE algorithm [3] was applied for protein interaction mapping. AlphaPulldown methodology was employed for protein complex prediction. Immunoprecipitation with LC-MS/MS detection was used for characterization of NF-κB factor RELA interactome. Results: The co-fractionation experiment led to identification of 5460 protein groups in total (FDR = 0.01) and to detection of 7568 interactions among 1520 protein groups. Of these, 2564 interactions have been validated in independent datasets. NF-κB modulation was associated with rearrangement of protein complexes involved in NF-κB signaling and immune response, cell cycle regulation and DNA replication. Central NF-κB transcription factor RELA co-eluted with interactors of NF-κB activator PRMT5, both established and new complexes were confirmed by AlphaPulldown prediction. A complementary immunoprecipitation experiment recapitulated RELA interactions with other NF-κB factors, and associated NF -κB inhibition with decreased binding of NF-κB activators to RELA. Conclusions: This study describes an extensive network of pro-tumorigenic NF-κB interactions and its rearrangement in breast cancer that may have a therapeutic implications in tumors with high NF-κB activity. References: 1. Bouchal P. et al.: Mol Cell Proteomics, 14(7):1814-30. (2015) 2. Kristensen A.R. et al.: Nat Methods, 9(9):907-9. (2012) 3. Stacey R.G. et al.: BMC Bioinformatics, 23;18(1):457 (2017)

Návaznosti

LX22NPO5102, projekt VaV

Název: Národní ústav pro výzkum rakoviny (Akronym: NÚVR)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro výzkum rakoviny, 5.1 EXCELES

Citovat

LAPČÍK, Petr, Greg R. STACEY, David POTĚŠIL, Leonard J. FOSTER a Pavel BOUCHAL. Global Interactome Mapping Reveals Pro-tumorigenic Interactions of NF-κB in Breast Cancer. In In Book of Abstracts of 22nd Human Proteome Organization World Congress, Busan, Korea 17.9.-21.9.2023, PP01.50. 2023.

@proceedings{2334197,
   author = {Lapčík, Petr and Stacey, Greg R. and Potěšil, David and Foster, Leonard J. and Bouchal, Pavel},
   booktitle = {In Book of Abstracts of 22nd Human Proteome Organization World Congress, Busan, Korea 17.9.-21.9.2023, PP01.50},
   keywords = {proteomics; NF-κB; Protein complexes; Breast cancer; Protein correlation profiling},
   language = {eng},
   title = {Global Interactome Mapping Reveals Pro-tumorigenic Interactions of NF-κB in Breast Cancer},
   url = {https://2023.hupo.org/wp-content/uploads/2023/09/Scientific-Program-Abstracts.pdf},
   year = {2023}
}

TY  - CONF
ID  - 2334197
AU  - Lapčík, Petr - Stacey, Greg R. - Potěšil, David - Foster, Leonard J. - Bouchal, Pavel
PY  - 2023
TI  - Global Interactome Mapping Reveals Pro-tumorigenic Interactions of NF-κB in Breast Cancer
KW  - proteomics
KW  - NF-κB
KW  - Protein complexes
KW  - Breast cancer
KW  - Protein correlation profiling
UR  - https://2023.hupo.org/wp-content/uploads/2023/09/Scientific-Program-Abstracts.pdf
N2  - Introduction: NF-κB pathway plays a key role in immune response and inflammation, however, our previous results supported by data from other studies show its role also in cancer development and progression, including lymph node metastasis of luminal A breast cancer [1]. Here we used size exclusion chromatography (SEC) fractionation and protein correlation profiling (PCP) [2] to study the impact of NF-κB modulation on global protein interactome dynamics in luminal A breast cancer model. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of 160 SEC fractions of native MCF-7 lysates with inhibited or innate NF-κB activity was performed and the PrInCE algorithm [3] was applied for protein interaction mapping. AlphaPulldown methodology was employed for protein complex prediction. Immunoprecipitation with LC-MS/MS detection was used for characterization of NF-κB factor RELA interactome. Results: The co-fractionation experiment led to identification of 5460 protein groups in total (FDR = 0.01) and to detection of 7568 interactions among 1520 protein groups. Of these, 2564 interactions have been validated in independent datasets. NF-κB modulation was associated with rearrangement of protein complexes involved in NF-κB signaling and immune response, cell cycle regulation and DNA replication. Central NF-κB transcription factor RELA co-eluted with interactors of NF-κB activator PRMT5, both established and new complexes were confirmed by AlphaPulldown prediction. A complementary immunoprecipitation experiment recapitulated RELA interactions with other NF-κB factors, and associated NF -κB inhibition with decreased binding of NF-κB activators to RELA. Conclusions: This study describes an extensive network of pro-tumorigenic NF-κB interactions and its rearrangement in breast cancer that may have a therapeutic implications in tumors with high NF-κB activity. References: 1. Bouchal P. et al.: Mol Cell Proteomics, 14(7):1814-30. (2015) 2. Kristensen A.R. et al.: Nat Methods, 9(9):907-9. (2012) 3. Stacey R.G. et al.: BMC Bioinformatics, 23;18(1):457 (2017)
ER  -

LAPČÍK, Petr, Greg R. STACEY, David POTĚŠIL, Leonard J. FOSTER a Pavel BOUCHAL. Global Interactome Mapping Reveals Pro-tumorigenic Interactions of NF-κB in Breast Cancer. In \textit{In Book of Abstracts of 22nd Human Proteome Organization World Congress, Busan, Korea 17.9.-21.9.2023, PP01.50}. 2023.

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