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  1. Article ; Online: Generation of three induced pluripotent stem cell lines from a patient with Kabuki syndrome carrying the KMT2D p.R4198X mutation.

    Lager, Tyson W / Zuo, Junjun / Alam, Md Suhail / Calhoun, Barbara / Haldar, Kasturi / Panopoulos, Athanasia D

    Stem cell research

    2022  Volume 62, Page(s) 102799

    Abstract: Kabuki syndrome (KS) is a rare genetic disorder typically characterized by facial abnormalities, developmental delay, cognitive dysfunction, and organ impairment. In this report, fibroblast cells obtained from a KS patient containing a heterozygous KMT2D ...

    Abstract Kabuki syndrome (KS) is a rare genetic disorder typically characterized by facial abnormalities, developmental delay, cognitive dysfunction, and organ impairment. In this report, fibroblast cells obtained from a KS patient containing a heterozygous KMT2D c.12592 C>T mutation (p.R4198X) were reprogrammed using non-integrative Sendai virus to generate three induced pluripotent stem cell (iPSC) clones. The iPSC lines retained the KS patient mutation, and displayed normal karyotypes, pluripotency marker expression, and the ability to differentiate into the three germ layers.
    MeSH term(s) Abnormalities, Multiple ; Face/abnormalities ; Hematologic Diseases/genetics ; Humans ; Induced Pluripotent Stem Cells ; Mutation/genetics ; Vestibular Diseases/genetics
    Language English
    Publishing date 2022-05-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2393143-7
    ISSN 1876-7753 ; 1873-5061
    ISSN (online) 1876-7753
    ISSN 1873-5061
    DOI 10.1016/j.scr.2022.102799
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A nanotherapeutic approach to selectively eliminate metastatic breast cancer cells by targeting cell surface GRP78.

    Shin, Jaeho / Kim, Baksun / Lager, Tyson W / Mejia, Franklin / Guldner, Ian / Conner, Clay / Zhang, Siyuan / Panopoulos, Athanasia D / Bilgicer, Basar

    Nanoscale

    2023  Volume 15, Issue 32, Page(s) 13322–13334

    Abstract: Here, rational engineering of doxorubicin prodrug loaded peptide-targeted liposomal nanoparticles to selectively target metastatic breast cancer ... ...

    Abstract Here, rational engineering of doxorubicin prodrug loaded peptide-targeted liposomal nanoparticles to selectively target metastatic breast cancer cells
    MeSH term(s) Animals ; Mice ; Endoplasmic Reticulum Chaperone BiP ; Membrane Proteins ; Cell Line, Tumor ; Prodrugs ; Glucose ; Peptides ; Doxorubicin/pharmacology ; Neoplasms
    Chemical Substances Endoplasmic Reticulum Chaperone BiP ; Membrane Proteins ; Prodrugs ; Glucose (IY9XDZ35W2) ; Peptides ; Doxorubicin (80168379AG)
    Language English
    Publishing date 2023-08-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2515664-0
    ISSN 2040-3372 ; 2040-3364
    ISSN (online) 2040-3372
    ISSN 2040-3364
    DOI 10.1039/d3nr00800b
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Cell surface GRP78 and Dermcidin cooperate to regulate breast cancer cell migration through Wnt signaling.

    Lager, Tyson W / Conner, Clay / Keating, Claudia R / Warshaw, Jane N / Panopoulos, Athanasia D

    Oncogene

    2021  Volume 40, Issue 23, Page(s) 4050–4059

    Abstract: The heat shock protein GRP78 typically resides in the endoplasmic reticulum in normal tissues, but it has been shown to be expressed on the cell surface of several cancer cells, and some stem cells, where it can act as a signaling molecule by not-yet- ... ...

    Abstract The heat shock protein GRP78 typically resides in the endoplasmic reticulum in normal tissues, but it has been shown to be expressed on the cell surface of several cancer cells, and some stem cells, where it can act as a signaling molecule by not-yet-fully defined mechanisms. Although cell surface GRP78 (sGRP78) has emerged as an attractive chemotherapeutic target, understanding how sGRP78 is functioning in cancer has been complicated by the fact that sGRP78 can function in a cell-context dependent manner, with a diverse array of reported binding partners, to regulate a variety of cellular responses. We had previously shown that sGRP78 was important in regulating pluripotent stem cell (PSC) functions, and hypothesized that embryonic-like mechanisms of GRP78 were critical to regulating aggressive breast cancer cell functions. Here, using proteomics we identify Dermcidin (DCD) as a novel sGRP78 binding partner common to both PSCs and breast cancer cells. We show that GRP78 and DCD cooperate to regulate stem cell and cancer cell migration that is dependent on the cell surface functions of these proteins. Finally, we identify Wnt/β-catenin signaling, a critical pathway in stem cell and cancer cell biology, as an important downstream intermediate in regulating this migration phenotype.
    MeSH term(s) Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Membrane/metabolism ; Cell Movement/physiology ; Cell Proliferation/physiology ; Endoplasmic Reticulum Chaperone BiP/metabolism ; Female ; Humans ; Peptides/metabolism ; Stem Cells/metabolism ; Wnt Signaling Pathway
    Chemical Substances Endoplasmic Reticulum Chaperone BiP ; HSPA5 protein, human ; Peptides ; dermcidin
    Language English
    Publishing date 2021-05-12
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 639046-8
    ISSN 1476-5594 ; 0950-9232
    ISSN (online) 1476-5594
    ISSN 0950-9232
    DOI 10.1038/s41388-021-01821-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Cell surface GRP78 promotes stemness in normal and neoplastic cells.

    Conner, Clay / Lager, Tyson W / Guldner, Ian H / Wu, Min-Zu / Hishida, Yuriko / Hishida, Tomoaki / Ruiz, Sergio / Yamasaki, Amanda E / Gilson, Robert C / Belmonte, Juan Carlos Izpisua / Gray, Peter C / Kelber, Jonathan A / Zhang, Siyuan / Panopoulos, Athanasia D

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 3474

    Abstract: Reliable approaches to identify stem cell mechanisms that mediate aggressive cancer could have great therapeutic value, based on the growing evidence of embryonic signatures in metastatic cancers. However, how to best identify and target stem-like ... ...

    Abstract Reliable approaches to identify stem cell mechanisms that mediate aggressive cancer could have great therapeutic value, based on the growing evidence of embryonic signatures in metastatic cancers. However, how to best identify and target stem-like mechanisms aberrantly acquired by cancer cells has been challenging. We harnessed the power of reprogramming to examine GRP78, a chaperone protein generally restricted to the endoplasmic reticulum in normal tissues, but which is expressed on the cell surface of human embryonic stem cells and many cancer types. We have discovered that (1) cell surface GRP78 (sGRP78) is expressed on iPSCs and is important in reprogramming, (2) sGRP78 promotes cellular functions in both pluripotent and breast cancer cells (3) overexpression of GRP78 in breast cancer cells leads to an induction of a CD24
    MeSH term(s) Animals ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Differentiation ; Cell Line, Tumor ; Cell Self Renewal ; Cell Transformation, Neoplastic ; Cellular Reprogramming ; Female ; HEK293 Cells ; Heat-Shock Proteins/antagonists & inhibitors ; Heat-Shock Proteins/genetics ; Heat-Shock Proteins/metabolism ; Humans ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/metabolism ; Lung Neoplasms/pathology ; Lung Neoplasms/secondary ; Mice ; Mice, Knockout ; Neoplastic Stem Cells/cytology ; Neoplastic Stem Cells/metabolism ; RNA Interference ; RNA, Small Interfering/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transplantation, Heterologous
    Chemical Substances Heat-Shock Proteins ; RNA, Small Interfering ; Transcription Factors ; molecular chaperone GRP78 (YCYIS6GADR)
    Language English
    Publishing date 2020-02-26
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-60269-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Sushi Domain Containing 2 (SUSD2) inhibits platelet activation and binding to high-grade serous ovarian carcinoma cells.

    Lager, Tyson W / Roetman, Jessica J / Kunkel, Jacob / Thacker, Megan / Sheets, Jordan N / Egland, Kristi A / Miles, Cecelia M / Larson, Mark K / Gubbels, Jennifer A A

    Platelets

    2018  Volume 29, Issue 8, Page(s) 834–837

    Abstract: Platelets play a central role in primary hemostasis affecting tumor survival and metastases. Tumors induce platelets to aggregate and bind to the cancer cells, resulting in protection from immune surveillance and often leading to thrombocytosis. In ... ...

    Abstract Platelets play a central role in primary hemostasis affecting tumor survival and metastases. Tumors induce platelets to aggregate and bind to the cancer cells, resulting in protection from immune surveillance and often leading to thrombocytosis. In ovarian cancer (OvCa), one-third of patients present with thrombocytosis, a diagnosis that correlates with shorter survival. SUSD2 (SUShi Domain containing 2), a type I transmembrane protein, shown to inhibit metastatic processes in high-grade serous ovarian carcinoma (HGSOC), is expressed on endothelial cells and thus may influence platelet reactivity. As such, we hypothesized that SUSD2 levels in ovarian cancer-derived cell lines influence platelet activation. We incubated OvCa non-targeting (NT) and SUSD2 knockdown (KD) cell lines with labeled platelets and quantified platelet binding, as well as GPIIb/IIIa integrin activation. The role of GPIIb/IIIa in tumor cell/platelet interaction was also examined by measuring cell-cell adhesion in the presence of eptifibatide. We found that platelets exposed to OvCa cells with low SUSD2 expression display increased tumor cell-platelet binding along with an increase in GPIIb/IIIa receptor activation. As such, platelet activation and binding to HGSOC cells was inversely correlated with the presence of SUSD2. This represents one of the first tumor proteins known to provide differential platelet interaction based on protein status.
    MeSH term(s) Blood Platelets/metabolism ; Blood Platelets/pathology ; Cell Adhesion ; Cell Line, Tumor ; Coculture Techniques ; Female ; Humans ; Membrane Glycoproteins/metabolism ; Neoplasm Proteins/metabolism ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Platelet Activation
    Chemical Substances Membrane Glycoproteins ; Neoplasm Proteins ; SUSD2 protein, human
    Language English
    Publishing date 2018-10-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 1034283-7
    ISSN 1369-1635 ; 0953-7104
    ISSN (online) 1369-1635
    ISSN 0953-7104
    DOI 10.1080/09537104.2018.1530345
    Database MEDical Literature Analysis and Retrieval System OnLINE

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