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  1. Article ; Online: Haldol Targets IQGAP1 Pathway and Promotes Novel Partner Interactions in Glioblastoma Cell Lines.

    Iyer, Varun J / Osman, Mahasin A

    microPublication biology

    2023  Volume 2023

    Abstract: Glioblastoma multiform (GBM) is an incurable heterogenous brain cancer with few clinical target options. IQGAP1 is a scaffold oncoprotein involved in GBM with unclear mechanism. Here we report that the antipsychotic drug Haldol differentially alters ... ...

    Abstract Glioblastoma multiform (GBM) is an incurable heterogenous brain cancer with few clinical target options. IQGAP1 is a scaffold oncoprotein involved in GBM with unclear mechanism. Here we report that the antipsychotic drug Haldol differentially alters IQGAP1 signaling and inhibits GBM cell proliferation, thus providing novel molecular signatures for GBM classification and potential targeted therapy in personalized medicine.
    Language English
    Publishing date 2023-05-08
    Publishing country United States
    Document type Journal Article
    ISSN 2578-9430
    ISSN (online) 2578-9430
    DOI 10.17912/micropub.biology.000822
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The Antipsychotic Drug Haldol Modulates IQGAP1-Signaling and Inhibits Cell Proliferation in Triple Negative Breast Cancer Cell Lines.

    Iyer, Varun J / Osman, Mahasin A

    microPublication biology

    2023  Volume 2023

    Abstract: The signaling scaffold oncoprotein IQGAP1 was identified as a classification and therapeutic biomarker in triple negative breast cancer (TNBC) cell lines. Here, we report that the antipsychotic drug Haldol induces novel protein-protein interactions with ... ...

    Abstract The signaling scaffold oncoprotein IQGAP1 was identified as a classification and therapeutic biomarker in triple negative breast cancer (TNBC) cell lines. Here, we report that the antipsychotic drug Haldol induces novel protein-protein interactions with IQGAP1 and inhibits cell proliferation in TNBC cell lines. The identified proteins share known functions of IQGAP1 in secretion, transcription and apoptosis and provide further classification tools and potential precision therapeutic targets for Haldol in TNBC.
    Language English
    Publishing date 2023-05-05
    Publishing country United States
    Document type Journal Article
    ISSN 2578-9430
    ISSN (online) 2578-9430
    DOI 10.17912/micropub.biology.000823
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: An Emerging Role for Sigma Receptor 1 in Personalized Treatment of Breast Cancer.

    Robinson, Taylor S / Osman, Mahasin A

    Cancers

    2023  Volume 15, Issue 13

    Abstract: Despite the major progress in treating breast cancer, recurrence remains a problem and types such as triple-negative breast cancer still lack targeted medicine. The orphan Sigma receptor1 (SigmaR1) has emerged as a target in breast cancer, but its ... ...

    Abstract Despite the major progress in treating breast cancer, recurrence remains a problem and types such as triple-negative breast cancer still lack targeted medicine. The orphan Sigma receptor1 (SigmaR1) has emerged as a target in breast cancer, but its mechanism of action is unclear and hinders clinical utility. SigmaR1 is widely expressed in organ tissues and localized to various sub-cellular compartments, particularly the endoplasmic reticulum (ER), the mitochondrial-associated membranes (MAMs) and the nuclear envelope. As such, it involves diverse cellular functions, including protein quality control/ER stress, calcium signaling, cholesterol homeostasis, mitochondrial integrity and energy metabolism. Consequently, SigmaR1 has been implicated in a number of cancers and degenerative diseases and thus has been intensively pursued as a therapeutic target. Because SigmaR1 binds a number of structurally unrelated ligands, it presents an excellent context-dependent therapeutic target. Here, we review its role in breast cancer and the current therapies that have been considered based on its known functions. As SigmaR1 is not classified as an oncoprotein, we propose a model in which it serves as an oligomerization adaptor in key cellular pathways, which may help illuminate its association with variable diseases and pave the way for clinical utility in personalized medicine.
    Language English
    Publishing date 2023-07-02
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15133464
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Characterization of a Novel IQGAP1-ADR-2 axis as a Target of Norepinephrine in Lung Cancer

    Tatiana Tatiana / Yusuf Barudi / Mahasin Osman

    Translation, Vol 11, Iss

    2023  Volume 3

    Keywords IQGAP1 ; ADRα-2 ; Norepinephrine ; lung cancer ; Adrenergic Receptor α-2a ; Medicine (General) ; R5-920
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher The University of Toledo
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Role of IQGAP1-Estrogen Receptor-AMPK Axis in the Sex Differences of Type 2 Diabetes

    Rawan Moussa / Alice Lu / Mahasin Osman

    Translation, Vol 11, Iss

    2023  Volume 3

    Keywords Sex differences in type 2 Diabetes ; IQGAP1 ; Estrogen receptor alpha ; AMPK ; Diabetes ; Endocrinology ; and Metabolism ; Research ; Medicine (General) ; R5-920
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher The University of Toledo
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Association between autoimmune diseases and glioblastoma

    Sadik Khuder, PhD / Nahshon A. Puente / Mahasin Osman

    Translation, Vol 11, Iss

    results from national inpatient database

    2023  Volume 3

    Keywords autoimmune ; glioblastoma ; HCUP ; Medicine (General) ; R5-920
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher The University of Toledo
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Role of Signal Dynamics in the Link Between Type 2 Diabetes and Cancer

    Mahasin Osman

    JOP Journal of the Pancreas, Vol 15, Iss 5, p

    2014  Volume 530

    Abstract: Epidemiological studies revealed a connection between several types of cancer and type 2 diabetes (T2D), and suggested that T2D is both a symptom and a risk factor of pancreatic cancer. High level of circulating insulin (hyperinsulinemia) associated with ...

    Abstract Epidemiological studies revealed a connection between several types of cancer and type 2 diabetes (T2D), and suggested that T2D is both a symptom and a risk factor of pancreatic cancer. High level of circulating insulin (hyperinsulinemia) associated with obesity has been implicated in promoting aggressive types of cancers. Peripheral insulin resistance, a symptom/risk factor of T2D, pressures pancreatic β-cells to increase insulin secretion, which results in hyperinsulinemia. This in turn, is believed to lead to a poorly understood gradual loss of functional β-cell mass, thus suggesting the existence of a fine-balance and interplay between β-cell function and mass. While the mechanisms of these connections are unclear, the mammalian target of rapamycin complex 1 (mTORC1) pathway has been implicated in controlling β-cell function and mass, and mediating a link between cancer and T2D.
    Keywords rapamycin ; hyperinsulinemia ; Medicine ; R ; Internal medicine ; RC31-1245 ; Specialties of internal medicine ; RC581-951 ; Diseases of the digestive system. Gastroenterology ; RC799-869
    Subject code 610
    Publishing date 2014-09-01T00:00:00Z
    Publisher E S Burioni Ricerche Bibliografiche
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: IQGAP1 control of centrosome function defines distinct variants of triple negative breast cancer.

    Osman, Mahasin A / Antonisamy, William James / Yakirevich, Evgeny

    Oncotarget

    2020  Volume 11, Issue 26, Page(s) 2493–2511

    Abstract: Triple negative breast cancer (TNBC) is a heterogenous and lethal disease that lacks diagnostic markers and therapeutic targets; as such common targets are highly sought after. IQGAP1 is a signaling scaffold implicated in TNBC, but its mechanism is ... ...

    Abstract Triple negative breast cancer (TNBC) is a heterogenous and lethal disease that lacks diagnostic markers and therapeutic targets; as such common targets are highly sought after. IQGAP1 is a signaling scaffold implicated in TNBC, but its mechanism is unknown. Here we show that IQGAP1 localizes to the centrosome, interacts with and influences the expression level and localization of key centrosome proteins like BRCA1 and thereby impacts centrosome number. Genetic mutant analyses suggest that phosphorylation cycling of IQGAP1 is important to its subcellular localization and centrosome-nuclear shuttling of BRCA1; dysfunction of this process defines two alternate mechanisms associated with cell proliferation. TNBC cell lines and patient tumor tissues differentially phenocopy these mechanisms supporting clinical existence of molecularly distinct variants of TNBC defined by IQGAP1 pathways. These variants are defined, at least in part, by differential mis-localization or stabilization of IQGAP1-BRCA1 and rewiring of a novel Erk1/2-MNK1-JNK-Akt-β-catenin signaling signature. We discuss a model in which IQGAP1 modulates centrosome-nuclear crosstalk to regulate cell division and imparts on cancer. These findings have implications on cancer racial disparities and can provide molecular tools for classification of TNBC, presenting IQGAP1 as a common target amenable to personalized medicine.
    Language English
    Publishing date 2020-06-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.27623
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: An Emerging Role for IQGAP1 in Regulating Protein Traffic

    Mahasin Osman

    The Scientific World Journal, Vol 10, Pp 944-

    2010  Volume 953

    Abstract: IQGAP1, an effector of CDC42p GTPase, is a widely conserved, multifunctional protein that bundles F-actin through its N-terminus and binds microtubules through its C-terminus to modulate the cell architecture. It has emerged as a potential oncogene ... ...

    Abstract IQGAP1, an effector of CDC42p GTPase, is a widely conserved, multifunctional protein that bundles F-actin through its N-terminus and binds microtubules through its C-terminus to modulate the cell architecture. It has emerged as a potential oncogene associated with diverse human cancers. Therefore, IQGAP1 has been heavily investigated; regardless, its precise cellular function remains unclear. Work from yeast suggests that IQGAP1 plays an important role in directed cell growth, which is a conserved feature crucial to morphogenesis, division axis, and body plan determination. New evidence suggests a conserved role for IQGAP1 in protein synthesis and membrane traffic, which may help to explain the diversity of its cellular functions. Membrane traffic mediates infections by intracellular pathogens and a range of degenerative human diseases arise from dysfunctions in intracellular traffic; thus, elucidating the mechanisms of cellular traffic will be important in order to understand the basis of a wide range of inherited and acquired human diseases. Recent evidence suggests that IQGAP1 plays its role in cell growth through regulating the conserved mTOR pathway. The mTOR signaling cascade has been implicated in membrane traffic and is activated in nearly all human cancers, but clinical response to the mTOR-specific inhibitor rapamycin has been disappointing. Thus, understanding the regulators of this pathway will be crucial in order to identify predictors of rapamycin sensitivity. In this review, I discuss emerging evidence that supports a potential role of IQGAP1 in regulating membrane traffic via regulating the mTOR pathway.
    Keywords Science (General) ; Q1-390
    Subject code 571
    Language English
    Publishing date 2010-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: An emerging role for IQGAP1 in regulating protein traffic.

    Osman, Mahasin

    TheScientificWorldJournal

    2010  Volume 10, Page(s) 944–953

    Abstract: IQGAP1, an effector of CDC42p GTPase, is a widely conserved, multifunctional protein that bundles F-actin through its N-terminus and binds microtubules through its C-terminus to modulate the cell architecture. It has emerged as a potential oncogene ... ...

    Abstract IQGAP1, an effector of CDC42p GTPase, is a widely conserved, multifunctional protein that bundles F-actin through its N-terminus and binds microtubules through its C-terminus to modulate the cell architecture. It has emerged as a potential oncogene associated with diverse human cancers. Therefore, IQGAP1 has been heavily investigated; regardless, its precise cellular function remains unclear. Work from yeast suggests that IQGAP1 plays an important role in directed cell growth, which is a conserved feature crucial to morphogenesis, division axis, and body plan determination. New evidence suggests a conserved role for IQGAP1 in protein synthesis and membrane traffic, which may help to explain the diversity of its cellular functions. Membrane traffic mediates infections by intracellular pathogens and a range of degenerative human diseases arise from dysfunctions in intracellular traffic; thus, elucidating the mechanisms of cellular traffic will be important in order to understand the basis of a wide range of inherited and acquired human diseases. Recent evidence suggests that IQGAP1 plays its role in cell growth through regulating the conserved mTOR pathway. The mTOR signaling cascade has been implicated in membrane traffic and is activated in nearly all human cancers, but clinical response to the mTOR-specific inhibitor rapamycin has been disappointing. Thus, understanding the regulators of this pathway will be crucial in order to identify predictors of rapamycin sensitivity. In this review, I discuss emerging evidence that supports a potential role of IQGAP1 in regulating membrane traffic via regulating the mTOR pathway.
    MeSH term(s) Actins/metabolism ; Cell Membrane/metabolism ; Cytoskeleton/metabolism ; Humans ; Protein Transport/physiology ; ras GTPase-Activating Proteins/physiology
    Chemical Substances Actins ; IQ motif containing GTPase activating protein 1 ; ras GTPase-Activating Proteins
    Language English
    Publishing date 2010-05-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2075968-X
    ISSN 1537-744X ; 1537-744X
    ISSN (online) 1537-744X
    ISSN 1537-744X
    DOI 10.1100/tsw.2010.85
    Database MEDical Literature Analysis and Retrieval System OnLINE

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