scholarly journals Epithelial cell extrusion requires the sphingosine-1-phosphate receptor 2 pathway

2011 ◽  
Vol 193 (4) ◽  
pp. 667-676 ◽  
Author(s):  
Yapeng Gu ◽  
Tetyana Forostyan ◽  
Roger Sabbadini ◽  
Jody Rosenblatt
Keyword(s):  
Stem Cells ◽  
Epithelial Cell ◽  
Kinase Activity ◽  
Apoptotic Cell ◽  
Sphingosine Kinase ◽  
Live Cells ◽  
Sphingosine 1 Phosphate ◽  
A Cell ◽  
Dying Cells ◽  
Cell Extrusion

To maintain an intact barrier, epithelia eliminate dying cells by extrusion. During extrusion, a cell destined for apoptosis signals its neighboring cells to form and contract a ring of actin and myosin, which squeezes the dying cell out of the epithelium. Here, we demonstrate that the signal produced by dying cells to initiate this process is sphingosine-1-phosphate (S1P). Decreasing S1P synthesis by inhibiting sphingosine kinase activity or by blocking extracellular S1P access to its receptor prevented apoptotic cell extrusion. Extracellular S1P activates extrusion by binding the S1P2 receptor in the cells neighboring a dying cell, as S1P2 knockdown in these cells or its loss in a zebrafish mutant disrupted cell extrusion. Because live cells can also be extruded, we predict that this S1P pathway may also be important for driving delamination of stem cells during differentiation or invasion of cancer cells.

Apoptotic cell extrusion depends on single-cell synthesis of sphingosine-1-phosphate by sphingosine kinase 2

2021 ◽  
Vol 1866 (4) ◽  
pp. 158888
Author(s):  
Bruno Jaime Santacreu ◽  
Daniela Judith Romero ◽  
Lucila Gisele Pescio ◽  
Estefanía Tarallo ◽  
Norma Beatriz Sterin-Speziale ◽  
...  
Keyword(s):  
Single Cell ◽  
Apoptotic Cell ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 2 ◽  
Sphingosine 1 Phosphate ◽  
Cell Synthesis ◽  
Cell Extrusion

scholarly journals Early Activation of Sphingosine Kinase in Mast Cells and Recruitment to FcεRI Are Mediated by Its Interaction with Lyn Kinase

2004 ◽  
Vol 24 (19) ◽  
pp. 8765-8777 ◽  
Author(s):  
Nicole Urtz ◽  
Ana Olivera ◽  
Elisa Bofill-Cardona ◽  
Robert Csonga ◽  
Andreas Billich ◽  
...  
Keyword(s):  
Mast Cells ◽  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Immunoglobulin E ◽  
Sphingosine Kinase ◽  
Lipid Kinase ◽  
Lyn Kinase ◽  
Sphingosine 1 Phosphate ◽  
High Affinity Receptor

ABSTRACT Sphingosine kinase has been recognized as an essential signaling molecule that mediates the intracellular conversion of sphingosine to sphingosine-1-phosphate. In mast cells, induction of sphingosine kinase and generation of sphingosine-1-phosphate have been linked to the initial rise in Ca2+, released from internal stores, and to degranulation. These events either precede or are concomitant with the activation of phospholipase C-γ and the generation of inositol trisphosphate. Here we show that sphingosine kinase type 1 (SPHK1) interacts directly with the tyrosine kinase Lyn and that this interaction leads to the recruitment of this lipid kinase to the high-affinity receptor for immunoglobulin E (FcεRI). The interaction of SPHK1 with Lyn caused enhanced lipid and tyrosine kinase activity. After FcεRI triggering, enhanced sphingosine kinase activity was associated with FcεRI in sphingolipid-enriched rafts of mast cells. Bone marrow-derived mast cells from Lyn−/ − mice, compared to syngeneic wild-type cells, were defective in the initial induction of SPHK1 activity, and the defect was overcome by retroviral Lyn expression. These findings position the activation of SPHK1 as an FcεRI proximal event.

scholarly journals Sphingosine Kinase 1 Signaling in Breast Cancer: A Potential Target to Tackle Breast Cancer Stem Cells

2021 ◽  
Vol 8 ◽  
Author(s):  
Ling-Wei Hii ◽  
Felicia Fei-Lei Chung ◽  
Chun-Wai Mai ◽  
Pei Yuen Ng ◽  
Chee-Onn Leong
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Signaling Axis ◽  
Sphingosine 1 Phosphate ◽  
Sphingosine Kinases ◽  
Research Findings

Sphingosine kinases (SPHKs) are conserved lipid enzymes that catalyze the formation of sphingosine-1-phosphate (S1P) through ATP-dependent phosphorylation of sphingosine. Two distinct SPHK isoforms, namely SPHK1 and SPHK2, have been identified to date, and the former has been implicated for its oncogenic roles in cancer development and progression. While SPHK1 signaling axis has been extensively studied in non-stem breast cancer cells, recent evidence has emerged to suggest a role of SPHK1 in regulating cancer stem cells (CSCs). With the clinical implications of CSCs in disease relapse and metastasis, it is believed that therapeutic approaches that can eradicate both non-stem cancer cells and CSCs could be a key to cancer cure. In this review, we first explore the oncogenic functions of sphingosine kinase 1 in human cancers and summarize current research findings of SPHK1 signaling with a focus on breast cancer. We also discuss the therapeutic potentials and perspectives of targeting SPHK1 signaling in breast cancer and cancer stem cells. We aim to offer new insights and inspire future studies looking further into the regulatory functions of SPHK1 in CSC-driven tumorigenesis, uncovering novel therapeutic avenues of using SPHK1-targeted therapy in the treatment of CSC-enriched refractory cancers.

scholarly journals Desmosomal coupling in apoptotic cell extrusion

2019 ◽  
Author(s):  
Minnah Thomas ◽  
Benoit Ladoux ◽  
Yusuke Toyama
Keyword(s):  
De Novo ◽  
Apoptotic Cell ◽  
Cell Junctions ◽  
Dead Cell ◽  
Mechanical Coupling ◽  
Physiological Processes ◽  
Actomyosin Contractility ◽  
Epithelial Sheet ◽  
Dying Cells ◽  
Cell Extrusion

SUMMARYThe mechanical coupling of epithelia enables coordination of tissue functions and collective tissue movements during different developmental and physiological processes. This coupling is ensured by cell-cell junctions, including adherens junctions (AJs) and desmosomal junctions (DJs) [1, 2]. During apoptosis, or programmed cell death, a dead cell is expelled from the tissue by coordinated processes between the dying cell and its neighbors. Apoptotic cell extrusion is driven by actomyosin cable formation and its contraction, and lamellipodial crawling of the neighboring cells (Fig. S1A-A’’, Movie S1) [3–6]. Throughout cell extrusion, the mechanical coupling of epithelia needs to be maintained in order to preserve tissue homeostasis [3]. Although much is known about the regulation of AJs in apoptotic cell extrusion [6–9], the role and dynamics of DJs during this process remains poorly understood. Here, we show that DJs stay intact throughout and are crucial for apoptotic cell extrusion. Pre-existing DJs between the apoptotic cell and neighboring non-dying cells remain intact even during the formation of de novo DJs between non-dying cells, suggesting that the neighboring cells possess two DJs in the middle of apoptotic cell extrusion. We further found that an actomyosin cable formed in the vicinity of DJs upon apoptosis, and subsequently deviated from DJs during its constriction. Interestingly, the departure of the actomyosin cable from DJs coincided with the timing when DJs lost their straightness, suggesting a release of junctional tension at DJs, and a mechanical coupling between DJs and actomyosin contractility. The depletion of desmoplakin, which links desmosomes and intermediate filaments, resulted in defective apical contraction and an inability to form de novo DJs, leading to a failure of apoptotic cell extrusion. Our study provides a framework to explain how desmosomes play pivotal roles in maintaining epithelial sheet integrity during apoptotic cell extrusion.

Regulation of the metabolism of apolipoprotein M and sphingosine 1-phosphate by hepatic PPARγ activity

2018 ◽  
Vol 475 (12) ◽  
pp. 2009-2024 ◽  
Author(s):  
Makoto Kurano ◽  
Hitoshi Ikeda ◽  
Naoyuki Iso-O ◽  
Masumi Hara ◽  
Kazuhisa Tsukamoto ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Mouse Liver ◽  
Kinase Activity ◽  
Sphingosine Kinase ◽  
Peroxisome Proliferator ◽  
Obese Mice ◽  
Peroxisome Proliferator Activated Receptor ◽  
Apolipoprotein M ◽  
Adenoviral Gene Transfer ◽  
Sphingosine 1 Phosphate

Apolipoprotein M (apoM) is a carrier and a modulator of sphingosine 1-phosphate (S1P), an important multifunctional bioactive lipid. Since peroxisome proliferator-activated receptor γ (PPARγ) is reportedly associated with the function and metabolism of S1P, we investigated the modulation of apoM/S1P homeostasis by PPARγ. First, we investigated the modulation of apoM and S1P homeostasis by the overexpression or knockdown of PPARγ in HepG2 cells and found that both the overexpression and the knockdown of PPARγ decreased apoM expression and S1P synthesis. When we activated or suppressed the PPARγ more mildly with pioglitazone or GW9662, we found that pioglitazone suppressed apoM expression and S1P synthesis, while GW9662 increased them. Next, we overexpressed PPARγ in mouse liver through adenoviral gene transfer and observed that both the plasma and hepatic apoM levels and the plasma S1P levels decreased, while the hepatic S1P levels increased, in the presence of enhanced sphingosine kinase activity. Treatment with pioglitazone decreased both the plasma and hepatic apoM and S1P levels only in diet-induced obese mice. Moreover, the overexpression of apoM increased, while the knockdown of apoM suppressed PPARγ activities in HepG2 cells. These results suggested that PPARγ regulates the S1P levels by modulating apoM in a bell-shaped manner, with the greatest levels of apoM/S1P observed when PPARγ was mildly expressed and that hepatic apoM/PPARγ axis might maintain the homeostasis of S1P metabolism.

scholarly journals Apoptotic cell-derived exosomes: messages from dying cells

2020 ◽  
Vol 52 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Ramesh Kakarla ◽  
Jaehark Hur ◽  
Yeon Ji Kim ◽  
Jaeyoung Kim ◽  
Yong-Joon Chwae
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Responses ◽  
Extracellular Vesicles ◽  
Apoptotic Cell ◽  
Active Form ◽  
Live Cells ◽  
Apoptotic Bodies ◽  
Pathological Conditions ◽  
Dying Cells

AbstractApoptosis, a type of programmed cell death that plays a key role in both healthy and pathological conditions, releases extracellular vesicles such as apoptotic bodies and microvesicles, but exosome release due to apoptosis is not yet commonly accepted. Here, the reports demonstrating the presence of apoptotic exosomes and their roles in inflammation and immune responses are summarized, together with a general summary of apoptosis and extracellular vesicles. In conclusion, apoptosis is not just a ‘silent’ type of cell death but an active form of communication from dying cells to live cells through exosomes.

Sphingosine 1-Phosphate and Sphingosine Kinase Activity during Chicken Embryonic Development

2007 ◽  
Vol 30 (4) ◽  
pp. 502-506 ◽  
Author(s):  
Chang-Hwan Choi ◽  
Ji-Seon Jeong ◽  
Bo-im Yoo ◽  
You-Xun Jin ◽  
Dong-Cheul Moon ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Kinase Activity ◽  
Sphingosine Kinase ◽  
Sphingosine 1 Phosphate
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