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  1. Article ; Online: NF-κB signaling in neoplastic transition from epithelial to mesenchymal phenotype.

    Oh, Amy / Pardo, Makayla / Rodriguez, Anaelena / Yu, Connie / Nguyen, Lisa / Liang, Olin / Chorzalska, Anna / Dubielecka, Patrycja M

    Cell communication and signaling : CCS

    2023  Volume 21, Issue 1, Page(s) 291

    Abstract: NF-κB transcription factors are critical regulators of innate and adaptive immunity and major mediators of inflammatory signaling. The NF-κB signaling is dysregulated in a significant number of cancers and drives malignant transformation through ... ...

    Abstract NF-κB transcription factors are critical regulators of innate and adaptive immunity and major mediators of inflammatory signaling. The NF-κB signaling is dysregulated in a significant number of cancers and drives malignant transformation through maintenance of constitutive pro-survival signaling and downregulation of apoptosis. Overactive NF-κB signaling results in overexpression of pro-inflammatory cytokines, chemokines and/or growth factors leading to accumulation of proliferative signals together with activation of innate and select adaptive immune cells. This state of chronic inflammation is now thought to be linked to induction of malignant transformation, angiogenesis, metastasis, subversion of adaptive immunity, and therapy resistance. Moreover, accumulating evidence indicates the involvement of NF-κB signaling in induction and maintenance of invasive phenotypes linked to epithelial to mesenchymal transition (EMT) and metastasis. In this review we summarize reported links of NF-κB signaling to sequential steps of transition from epithelial to mesenchymal phenotypes. Understanding the involvement of NF-κB in EMT regulation may contribute to formulating optimized therapeutic strategies in cancer. Video Abstract.
    MeSH term(s) Humans ; NF-kappa B/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Signal Transduction ; Neoplasms/metabolism ; Cell Transformation, Neoplastic ; Phenotype ; Cell Line, Tumor
    Chemical Substances NF-kappa B
    Language English
    Publishing date 2023-10-18
    Publishing country England
    Document type Video-Audio Media ; Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2126315-2
    ISSN 1478-811X ; 1478-811X
    ISSN (online) 1478-811X
    ISSN 1478-811X
    DOI 10.1186/s12964-023-01207-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Proximity proteomics reveals role of Abelson interactor 1 in the regulation of TAK1/RIPK1 signaling.

    Petersen, Max / Chorzalska, Anna / Pardo, Makayla / Rodriguez, Anaelena / Morgan, John / Ahsan, Nagib / Zhao, Ting C / Liang, Olin / Kotula, Leszek / Bertone, Paul / Gruppuso, Philip A / Dubielecka, Patrycja M

    Molecular oncology

    2023  Volume 17, Issue 11, Page(s) 2356–2379

    Abstract: Dysregulation of the adaptor protein Abelson interactor 1 (ABI1) is linked to malignant transformation. To interrogate the role of ABI1 in cancer development, we mapped the ABI1 interactome using proximity-dependent labeling (PDL) with biotin followed by ...

    Abstract Dysregulation of the adaptor protein Abelson interactor 1 (ABI1) is linked to malignant transformation. To interrogate the role of ABI1 in cancer development, we mapped the ABI1 interactome using proximity-dependent labeling (PDL) with biotin followed by mass spectrometry. Using a novel PDL data filtering strategy, considering both peptide spectral matches and peak areas of detected peptides, we identified 212 ABI1 proximal interactors. These included WAVE2 complex components such as CYFIP1, NCKAP1, or WASF1, confirming the known role of ABI1 in the regulation of actin-polymerization-dependent processes. We also identified proteins associated with the TAK1-IKK pathway, including TAK1, TAB2, and RIPK1, denoting a newly identified function of ABI1 in TAK1-NF-κB inflammatory signaling. Functional assays using TNFα-stimulated, ABI1-overexpressing or ABI1-deficient cells showed effects on the TAK1-NF-kB pathway-dependent signaling to RIPK1, with ABI1-knockout cells being less susceptible to TNFα-induced, RIPK1-mediated, TAK1-dependent apoptosis. In sum, our PDL-based strategy enabled mapping of the ABI1 proximal interactome, thus revealing a previously unknown role of this adaptor protein in TAK1/RIPK1-based regulation of cell death and survival.
    MeSH term(s) Humans ; Tumor Necrosis Factor-alpha/pharmacology ; Tumor Necrosis Factor-alpha/metabolism ; Proteomics ; Signal Transduction ; NF-kappa B/metabolism ; Apoptosis/physiology ; Receptor-Interacting Protein Serine-Threonine Kinases/genetics ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Cytoskeletal Proteins/metabolism ; Wiskott-Aldrich Syndrome Protein Family/metabolism
    Chemical Substances Tumor Necrosis Factor-alpha ; NF-kappa B ; RIPK1 protein, human (EC 2.7.11.1) ; Receptor-Interacting Protein Serine-Threonine Kinases (EC 2.7.11.1) ; TAB2 protein, human ; Adaptor Proteins, Signal Transducing ; ABI1 protein, human ; Cytoskeletal Proteins ; WASF1 protein, human ; Wiskott-Aldrich Syndrome Protein Family
    Language English
    Publishing date 2023-05-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2415106-3
    ISSN 1878-0261 ; 1574-7891
    ISSN (online) 1878-0261
    ISSN 1574-7891
    DOI 10.1002/1878-0261.13374
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Transcriptomics of acute myeloid leukaemia core bone marrow biopsies reveals distinct therapy response-specific osteo-mesenchymal profiles.

    Treaba, Diana O / Bonal, Dennis M / Chorzalska, Anna / Castillo-Martin, Mireia / Oakes, Alissa / Pardo, Makayla / Petersen, Max / Schorl, Christoph / Hopkins, Kelsey / Melcher, Dean / Zhao, Ting C / Liang, Olin / So, Eui-Young / Reagan, John / Olszewski, Adam J / Butera, James / Anthony, Douglas C / Rintels, Peter / Quesenberry, Peter /
    Dubielecka, Patrycja M

    British journal of haematology

    2022  Volume 200, Issue 6, Page(s) 740–754

    Abstract: While the bone marrow (BM) microenvironment is significantly remodelled in acute myeloid leukaemia (AML), molecular insight into AML-specific alterations in the microenvironment has been historically limited by the analysis of liquid marrow aspirates ... ...

    Abstract While the bone marrow (BM) microenvironment is significantly remodelled in acute myeloid leukaemia (AML), molecular insight into AML-specific alterations in the microenvironment has been historically limited by the analysis of liquid marrow aspirates rather than core biopsies that contain solid-phase BM stroma. We assessed the effect of anthracycline- and cytarabine-based induction chemotherapy on both haematopoietic and non-haematopoietic cells directly in core BM biopsies using RNA-seq and histological analysis. We compared matched human core BM biopsies at diagnosis and 2 weeks after cytarabine- and anthracycline-based induction therapy in responders (<5% blasts present after treatment) and non-responders (≥5% blasts present after treatment). Our data indicated enrichment in vimentin (VIM), platelet-derived growth factor receptor beta (PDGFRB) and Snail family transcriptional repressor 2 (SNAI2) transcripts in responders, consistent with the reactivation of the mesenchymal population in the BM stroma. Enrichment of osteoblast maturation-related transcripts of biglycan (BGN), osteopontin (SPP1) and osteonectin (SPARC) was observed in non-responders. To the best of our knowledge, this is the first report demonstrating distinct osteogenic and mesenchymal transcriptome profiles specific to AML response to induction chemotherapy assessed directly in core BM biopsies. Detailing treatment response-specific alterations in the BM stroma may inform optimised therapeutic strategies for AML.
    MeSH term(s) Humans ; Bone Marrow/pathology ; Transcriptome ; Leukemia, Myeloid, Acute/drug therapy ; Cytarabine/therapeutic use ; Bone Marrow Cells/pathology ; Anthracyclines/therapeutic use ; Biopsy ; Tumor Microenvironment
    Chemical Substances Cytarabine (04079A1RDZ) ; Anthracyclines
    Language English
    Publishing date 2022-11-10
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.18513
    Database MEDical Literature Analysis and Retrieval System OnLINE

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