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Articles 1 - 9 of 9
Full-Text Articles in Cell and Developmental Biology
Vegf/Neuropilin Signaling In Cancer Stem Cells, Arthur M. Mercurio
Vegf/Neuropilin Signaling In Cancer Stem Cells, Arthur M. Mercurio
Arthur M. Mercurio
The function of vascular endothelial growth factor (VEGF) in cancer extends beyond angiogenesis and vascular permeability. Specifically, VEGF-mediated signaling occurs in tumor cells and this signaling contributes to key aspects of tumorigenesis including the self-renewal and survival of cancer stem cells (CSCs). In addition to VEGF receptor tyrosine kinases, the neuropilins (NRPs) are critical for mediating the effects of VEGF on CSCs, primarily because of their ability to impact the function of growth factor receptors and integrins. VEGF/NRP signaling can regulate the expression and function of key molecules that have been implicated in CSC function including Rho family guanosine triphosphatases …
Inhibition Of Triggering Receptor Expressed On Myeloid Cells 1 Ameliorates Inflammation And Macrophage And Neutrophil Activation In Alcoholic Liver Disease In Mice, David Tornai, Istvan Furi, Zu T. Shen, Alexander B. Sigalov, Sahin Coban, Gyongyi Szabo
Inhibition Of Triggering Receptor Expressed On Myeloid Cells 1 Ameliorates Inflammation And Macrophage And Neutrophil Activation In Alcoholic Liver Disease In Mice, David Tornai, Istvan Furi, Zu T. Shen, Alexander B. Sigalov, Sahin Coban, Gyongyi Szabo
Gyongyi Szabo
Alcoholic liver disease (ALD) is characterized by macrophage and neutrophil leukocyte recruitment and activation in the liver. Damage- and pathogen-associated molecular patterns contribute to a self-perpetuating proinflammatory state in ALD. Triggering receptor expressed on myeloid cells 1 (TREM-1) is a surface receptor that amplifies inflammation induced by toll-like receptors (TLRs) and is expressed on neutrophils and monocytes/macrophages. We hypothesized that TREM-1 signaling contributes to proinflammatory pathway activation in ALD. Using an in vivo ALD model in mice, we tested the effects of ligand-independent TREM-1 inhibitory peptides that were formulated into human high-density lipoprotein (HDL)-mimicking complexes GF9-HDL and GA/E31-HDL. As revealed …
Constitutive Interferon Signaling Maintains Critical Threshold Of Mlkl Expression To License Necroptosis, Joseph Sarhan, Beiyun C. Liu, Hayley I. Muendlein, Chi G. Weindel, Irina Smirnova, Amy Y. Tang, Vladimir Ilyukha, Maxim Sorokin, Anton Buzdin, Katherine A. Fitzgerald, Alexander Poltorak
Constitutive Interferon Signaling Maintains Critical Threshold Of Mlkl Expression To License Necroptosis, Joseph Sarhan, Beiyun C. Liu, Hayley I. Muendlein, Chi G. Weindel, Irina Smirnova, Amy Y. Tang, Vladimir Ilyukha, Maxim Sorokin, Anton Buzdin, Katherine A. Fitzgerald, Alexander Poltorak
Katherine A. Fitzgerald
Interferons (IFNs) are critical determinants in immune-competence and autoimmunity, and are endogenously regulated by a low-level constitutive feedback loop. However, little is known about the functions and origins of constitutive IFN. Recently, lipopolysaccharide (LPS)-induced IFN was implicated as a driver of necroptosis, a necrotic form of cell death downstream of receptor-interacting protein (RIP) kinase activation and executed by mixed lineage kinase like-domain (MLKL) protein. We found that the pre-established IFN status of the cell, instead of LPS-induced IFN, is critical for the early initiation of necroptosis in macrophages. This pre-established IFN signature stems from cytosolic DNA sensing via cGAS/STING, and …
Prostate Tumorigenesis Induced By Pten Deletion Involves Estrogen Receptor Beta Repression, Paul Mak, Jianrong Li, Sanjoy Samanta, Cheng Chang, D. Joseph Jerry, Roger J. Davis, Irwin Leav, Arthur M. Mercurio
Prostate Tumorigenesis Induced By Pten Deletion Involves Estrogen Receptor Beta Repression, Paul Mak, Jianrong Li, Sanjoy Samanta, Cheng Chang, D. Joseph Jerry, Roger J. Davis, Irwin Leav, Arthur M. Mercurio
Arthur M. Mercurio
The role of ERbeta in prostate cancer is unclear, although loss of ERbeta is associated with aggressive disease. Given that mice deficient in ERbeta do not develop prostate cancer, we hypothesized that ERbeta loss occurs as a consequence of tumorigenesis caused by other oncogenic mechanisms and that its loss is necessary for tumorigenesis. In support of this hypothesis, we found that ERbeta is targeted for repression in prostate cancer caused by PTEN deletion and that loss of ERbeta is important for tumor formation. ERbeta transcription is repressed by BMI-1, which is induced by PTEN deletion and important for prostate tumorigenesis. …
A Laminin 511 Matrix Is Regulated By Taz And Functions As The Ligand For The Alpha6bbeta1 Integrin To Sustain Breast Cancer Stem Cells, Cheng Chang, Hira Lal Goel, Huijie Gao, Bryan M. Pursell, Leonard D. Shultz, Dale L. Greiner, Sulev Ingerpuu, Manuel Patarroyo, Shiliang Cao, Elgene Lim, Junhao Mao, Karen Kulju. Mckee, Peter D. Yurchenco, Arthur M. Mercurio
A Laminin 511 Matrix Is Regulated By Taz And Functions As The Ligand For The Alpha6bbeta1 Integrin To Sustain Breast Cancer Stem Cells, Cheng Chang, Hira Lal Goel, Huijie Gao, Bryan M. Pursell, Leonard D. Shultz, Dale L. Greiner, Sulev Ingerpuu, Manuel Patarroyo, Shiliang Cao, Elgene Lim, Junhao Mao, Karen Kulju. Mckee, Peter D. Yurchenco, Arthur M. Mercurio
Arthur M. Mercurio
Understanding how the extracellular matrix impacts the function of cancer stem cells (CSCs) is a significant but poorly understood problem. We report that breast CSCs produce a laminin (LM) 511 matrix that promotes self-renewal and tumor initiation by engaging the alpha6Bbeta1 integrin and activating the Hippo transducer TAZ. Although TAZ is important for the function of breast CSCs, the mechanism is unknown. We observed that TAZ regulates the transcription of the alpha5 subunit of LM511 and the formation of a LM511 matrix. These data establish a positive feedback loop involving TAZ and LM511 that contributes to stemness in breast cancer.
Human Umbilical Cord Blood-Derived Mononuclear Cells Improve Murine Ventricular Function Upon Intramyocardial Delivery In Right Ventricular Chronic Pressure Overload, Saji Oommen, Satsuki Yamada, Susana Cantero Peral, Katherine A. Campbell, Elizabeth S. Bruinsma, Andre Terzic, Timothy J. Nelson
Human Umbilical Cord Blood-Derived Mononuclear Cells Improve Murine Ventricular Function Upon Intramyocardial Delivery In Right Ventricular Chronic Pressure Overload, Saji Oommen, Satsuki Yamada, Susana Cantero Peral, Katherine A. Campbell, Elizabeth S. Bruinsma, Andre Terzic, Timothy J. Nelson
Katherine Campbell, PhD
No abstract provided.
Regulated Splicing Of The Alpha6 Integrin Cytoplasmic Domain Determines The Fate Of Breast Cancer Stem Cells, Hira Lal Goel, Tatiana Gritsko, Bryan Pursell, Cheng Chang, Leonard D. Shultz, Dale L. Greiner, Jens Henrik Norum, Rune Toftgard, Leslie M. Shaw, Arthur M. Mercurio
Regulated Splicing Of The Alpha6 Integrin Cytoplasmic Domain Determines The Fate Of Breast Cancer Stem Cells, Hira Lal Goel, Tatiana Gritsko, Bryan Pursell, Cheng Chang, Leonard D. Shultz, Dale L. Greiner, Jens Henrik Norum, Rune Toftgard, Leslie M. Shaw, Arthur M. Mercurio
Arthur M. Mercurio
Although the alpha6beta1 integrin has been implicated in the function of breast and other cancer stem cells (CSCs), little is known about its regulation and relationship to mechanisms involved in the genesis of CSCs. We report that a CD44(high)/CD24(low) population, enriched for CSCs, is comprised of distinct epithelial and mesenchymal populations that differ in expression of the two alpha6 cytoplasmic domain splice variants: alpha6A and alpha6B. alpha6Bbeta1 expression defines the mesenchymal population and is necessary for CSC function, a function that cannot be executed by alpha6A integrins. The generation of alpha6Bbeta1 is tightly controlled and occurs as a consequence of …
Novel Developmental Biology-Based Protocol Of Embryonic Stem Cell Differentiation To Morphologically Sound And Functional Yet Immature Hepatocytes, Terence Bukong, Tracie Lo, Gyongyi Szabo, Angela Dolganiuc
Novel Developmental Biology-Based Protocol Of Embryonic Stem Cell Differentiation To Morphologically Sound And Functional Yet Immature Hepatocytes, Terence Bukong, Tracie Lo, Gyongyi Szabo, Angela Dolganiuc
Gyongyi Szabo
BACKGROUND/AIMS: Liver diseases are common in the United States and often require liver transplantation; however, donated organs are limited and thus alternative sources for liver cells are in high demand. Embryonic stem cells (ESC) can provide a continuous and readily available source of liver cells. ESC differentiation to liver cells is yet to be fully understood and comprehensive differentiation protocols are yet to be defined. Here, we aimed to achieve human (h)ESC differentiation into mature hepatocytes using defined recombinant differentiation factors and metabolites. METHODS: Embryonic stem cell H1 line was sub-cultured on feeder layer. We induced hESCs into endodermal differentiation …
Endothelial Cell Cortactin Phosphorylation By Src Contributes To Polymorphonuclear Leukocyte Transmigration In Vitro, L. Yang, Jennifer R. Kowalski, X. Zhan, S. M. Thomas, F. W. Luscinskas
Endothelial Cell Cortactin Phosphorylation By Src Contributes To Polymorphonuclear Leukocyte Transmigration In Vitro, L. Yang, Jennifer R. Kowalski, X. Zhan, S. M. Thomas, F. W. Luscinskas
Jennifer Kowalski
The underlying mechanisms that regulate leukocyte transendothelial migration through the vascular endothelium remain unclear. Cortactin is a substrate of Src tyrosine kinases and a regulator of cytoskeletal dynamics. Previous studies demonstrated a role for Src phosphorylation of cortactin in clustering of E-selectin and intercellular cell adhesion molecule-1 around adherent leukocytes. In the current study, we used an in vitro flow model to investigate the role of Src-induced cortactin phosphorylation in endothelium during polymorphonuclear leukocyte (PMN) transmigration through human umbilical vein endothelium (HUVEC) monolayers preactivated with tumor necrosis factor-{alpha}. Inhibition of Src in HUVEC using Src kinase inhibitors PP2 and SU6656 …