scholarly journals Class II phosphoinositide 3-kinase defines a novel signaling pathway in cell migration

2005 ◽  
Vol 169 (5) ◽  
pp. 789-799 ◽  
Author(s):  
Tania Maffucci ◽  
Frank T. Cooke ◽  
Fiona M. Foster ◽  
Colin J. Traer ◽  
Michael J. Fry ◽  
...  
Keyword(s):  
Cell Migration ◽  
Signaling Pathway ◽  
Lysophosphatidic Acid ◽  
Second Messenger ◽  
Cellular Responses ◽  
Class Ii ◽  
Downstream Effectors ◽  
Phosphoinositide 3 Kinase ◽  
Precise Role

The lipid products of phosphoinositide 3-kinase (PI3K) are involved in many cellular responses such as proliferation, migration, and survival. Disregulation of PI3K-activated pathways is implicated in different diseases including cancer and diabetes. Among the three classes of PI3Ks, class I is the best characterized, whereas class II has received increasing attention only recently and the precise role of these isoforms is unclear. Similarly, the role of phosphatidylinositol-3-phosphate (PtdIns-3-P) as an intracellular second messenger is only just beginning to be appreciated. Here, we show that lysophosphatidic acid (LPA) stimulates the production of PtdIns-3-P through activation of a class II PI3K (PI3K-C2β). Both PtdIns-3-P and PI3K-C2β are involved in LPA-mediated cell migration. This study is the first identification of PtdIns-3-P and PI3K-C2β as downstream effectors in LPA signaling and demonstration of an intracellular role for a class II PI3K. Defining this novel PI3K-C2β–PtdIns-3-P signaling pathway may help clarify the process of cell migration and may shed new light on PI3K-mediated intracellular events.

scholarly journals Impaired platelet responses to thrombin and collagen in AKT-1–deficient mice

Blood ◽  
2004 ◽  
Vol 104 (6) ◽  
pp. 1703-1710 ◽  
Author(s):  
Juhua Chen ◽  
Sarmishtha De ◽  
Derek S. Damron ◽  
William S. Chen ◽  
Nissim Hay ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Ex Vivo ◽  
Dense Granules ◽  
Fibrinogen Binding ◽  
Downstream Effectors ◽  
Low Concentrations ◽  
Phosphoinositide 3 Kinase ◽  
Deficient Mice ◽  
Granule Release

Abstract We investigated the role of Akt-1, one of the major downstream effectors of phosphoinositide 3-kinase (PI3K), in platelet function using mice in which the gene for Akt-1 had been inactivated. Using ex vivo techniques, we showed that Akt-1-deficient mice exhibited impaired platelet aggregation and spreading in response to various agonists. These differences were most apparent in platelets activated with low concentrations of thrombin. Although Akt-1 is not the predominant Akt isoform in mouse platelets, its absence diminished the amount of total phospho-Akt and inhibited increases in intracellular Ca2+ concentration in response to thrombin. Moreover, thrombin-induced platelet α-granule release as well as release of adenosine triphosphate from dense granules was also defective in Akt-1-null platelets. Although the absence of Akt-1 did not influence expression of the major platelet receptors for thrombin and collagen, fibrinogen binding in response to these agonists was significantly reduced. As a consequence of impaired αIIbβ3 activation and platelet aggregation, Akt-1 null mice showed significantly longer bleeding times than wild-type mice. (Blood. 2004;104:1703-1710)

scholarly journals NLRC5 promotes cell migration and invasion by activating the PI3K/AKT signaling pathway in endometrial cancer

2020 ◽  
Vol 48 (5) ◽  
pp. 030006052092535
Author(s):  
Yijun Fan ◽  
Zhen Dong ◽  
Yuchuan Shi ◽  
Shiying Sun ◽  
Bing Wei ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cell Migration ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Positive Role ◽  
Normal Endometrium ◽  
Cell Migration And Invasion

Objective NOD-like receptor family caspase recruitment domain family domain-containing 5 (NLRC5) is involved in the development of cancer. Our objective was to explore the role of NLRC5 in the progression of endometrial cancer (EC). Methods The roles of NLRC5 in migration and invasion of AN3CA EC cells were examined by cell wound-healing assay, Transwell migration, and invasion analysis. Overexpression of NLRC5 was achieved with NLRC5 plasmid, and knockdown of NLRC5 was achieved using small interfering (si)RNA-NLRC5 in AN3CA cells. The expression of NLRC5 was detected by immunohistochemical, western blot, and quantitative real-time PCR. LY294002 was used to inhibit the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. Results NLRC5 was downregulated in EC tissue compared with normal endometrium. Overexpression of NLRC5 led to upregulation of cell migration and invasion in AN3CA cells and expression of matrix metallopeptidase (MMP)-9. Inhibition of NLRC5 restricted migration and invasion of AN3CA cells and expression of MMP9. Overexpression of NLRC5 promoted the activation of PI3K/AKT signaling pathway. Inhibiting PI3K/AKT signaling pathway by using LY294002 blocked the positive role of NLRC5 in migration and invasion of AN3CA cells and expression of MMP9. Conclusions These results demonstrate that NLRC5 promotes EC progression by activating the PI3K/AKT signaling pathway.

scholarly journals Inhibitory role of polyunsaturated fatty acids on lysophosphatidic acid-induced cancer cell migration and adhesion

FEBS Letters ◽  
2014 ◽  
Vol 588 (17) ◽  
pp. 2971-2977 ◽  
Author(s):  
Eun Kyoung Kim ◽  
Jung Min Ha ◽  
Young Whan Kim ◽  
Seo Yeon Jin ◽  
Hong Koo Ha ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cell Migration ◽  
Polyunsaturated Fatty Acids ◽  
Cancer Cell ◽  
Lysophosphatidic Acid ◽  
Cancer Cell Migration ◽  
Inhibitory Role

Dexmedetomidine Inhibited Proliferation and Invasion of Cervical Cancer Cells by Inhibiting the Janus Tyrosine Kinase/Signal Transducer and Activator of Transcription Signaling Pathway

2021 ◽  
Vol 11 (7) ◽  
pp. 1293-1304
Author(s):  
FenLan Xu ◽  
Liying Xu ◽  
Xiaoyan Xu ◽  
Zhenhua Huang ◽  
Liang Su
Keyword(s):  
Cervical Cancer ◽  
Cell Migration ◽  
Western Blot ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Stat Signaling ◽  
Related Proteins

The role of anesthetics in the treatment of cancer has been reported, but the role of Dexmedetomidine (Dex) in the treatment of cervical cancer (CC) has not been reported.In this study, cell viability and proliferation were determined by MTT and cloning formation assay. The expression of proliferation-related proteins ki67 and PCNA was detected by western blot. Wound healing and transwell detected cell migration and invasion, and western blot detected the expression of migration and invasion related proteins MMP4 and MMP9, and epithelial-mesenchymal transformation (ETM)-related proteins N-cadherin, Snail, Vimentin and E-cadherin. Western blot also detected the expression of pathway related proteins p-JAK2, p-STAT1, p-STAT3, JAK2, STAT1 and STAT3. It showed that Dex inhibited the cell viability and proliferation of Hela and siHa and the expression of ki67 and PCNA were also inhibited. Dex inhibited the cell migration and invasion, and inhibited the expression of MMP4 and MMP9. In addition, Dex inhibited the expression of N-cadherin, Snail and Vimentin, and promoted the expression of E-cadherin. Dex inhibited the expression of p-JAK2, p-STAT1 and p-STAT3. After the addition of JAK/STAT signaling pathway agonist IL-6, the inhibition of Dex on proliferation, migration and invasion of CC cells was reversed. And the addition of JAK/STAT signaling pathway inhibitor AG490 could counteract the excitatory effect of IL-6 on the pathway, at which time the cell proliferation, invasion and migration were significantly increased. In conclusion, our study demonstrated that Dex inhibited proliferation, migration, and invasion of cells in CC by blocking the JAK/STAT signaling pathway.

scholarly journals The G12/13-RhoA signaling pathway contributes to efficient lysophosphatidic acid-stimulated cell migration

Oncogene ◽  
2005 ◽  
Vol 25 (15) ◽  
pp. 2234-2244 ◽  
Author(s):  
D Bian ◽  
C Mahanivong ◽  
J Yu ◽  
S M Frisch ◽  
Z K Pan ◽  
...  
Keyword(s):  
Cell Migration ◽  
Signaling Pathway ◽  
Lysophosphatidic Acid ◽  
Rhoa Signaling

scholarly journals Lysophosphatidic acid attenuates the cytotoxic effects and degree of peroxisome proliferator-activated receptor γ activation induced by 15-deoxyΔ12,14-prostaglandin J2 in neuroblastoma cells

2004 ◽  
Vol 382 (1) ◽  
pp. 83-91 ◽  
Author(s):  
Helen A. RODWAY ◽  
Alan N. HUNT ◽  
Janice A. KOHLER ◽  
Anthony D. POSTLE ◽  
Karen A. LILLYCROP
Keyword(s):  
Cell Death ◽  
Growth Inhibition ◽  
Lysophosphatidic Acid ◽  
Serum Lipid ◽  
Neuroblastoma Cells ◽  
Cellular Responses ◽  
Complete Medium ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Phosphoinositide 3 Kinase

PPARγ (peroxisome proliferator-activated receptor γ) is a ligand-activated transcription factor that responds to 15dPGJ2 (15-deoxy-Δ12,14-prostglandin J2). 15dPGJ2, in vitro, halts neuroblastoma cell growth, but reported mechanisms vary. Here we evaluated the modulatory effects of endogenous serum lipid mitogens upon the extent of 15dPGJ2-induced growth inhibition and on the precise cellular responses of neuroblastoma cells to PPARγ activation. We show that 15dPGJ2 specifically inhibited cell growth in both complete and delipidated media. 15dPGJ2-induced growth inhibition was accompanied by decreased cell viability, although the effect was far more marked in delipidated medium than in complete medium. Incubation with 15dPGJ2 in complete medium resulted in cytoplasmic changes characteristic of type II programmed cell death (autophagy), while prior serum lipid removal resulted in cell death via an apoptotic mechanism. These distinct, serum lipid-dependent cellular responses to 15dPGJ2 were accompanied by increases in the expression of a reporter gene construct containing a PPAR response element of 2.3-fold in complete medium, but of 4.8-fold in delipidated medium. Restoration of the serum lysolipid LPA (lysophosphatidic acid) to cells in delipidated medium reduced 15dPGJ2-mediated PPARγ activation, growth inhibition and cell death; following addition of S1P (sphingosine 1-phosphate), decreases were apparent but more marginal. Further, while the effects of LPA in delipidated medium were mediated through a Gi/phosphoinositide 3-kinase/MAPK (mitogen-activated protein kinase) pathway, those of S1P did not involve the MAPK component. These data suggest that the serum lysolipid LPA modulates the degree of PPARγ activation and the precise cellular response to 15dPGJ2 via activation of a Gi/phosphoinositide 3-kinase/MAPK pathway.

The class II phosphoinositide 3-kinase PI3K-C2β regulates cell migration by a PtdIns(3)P dependent mechanism

2005 ◽  
Vol 205 (3) ◽  
pp. 452-462 ◽  
Author(s):  
Jan Domin ◽  
Lisa Harper ◽  
Deborah Aubyn ◽  
Matthew Wheeler ◽  
Oliver Florey ◽  
...  
Keyword(s):  
Cell Migration ◽  
Class Ii ◽  
Phosphoinositide 3 Kinase ◽  
Dependent Mechanism

scholarly journals Phosphoinositide 3-Kinase C2β Regulates Cytoskeletal Organization and Cell Migration via Rac-dependent Mechanisms

2006 ◽  
Vol 17 (9) ◽  
pp. 3729-3744 ◽  
Author(s):  
Roy M. Katso ◽  
Olivier E. Pardo ◽  
Andrea Palamidessi ◽  
Clemens M. Franz ◽  
Marin Marinov ◽  
...  
Keyword(s):  
Cell Migration ◽  
Molecular Mechanisms ◽  
Egf Receptor ◽  
Human Tumor ◽  
Class Ii ◽  
Dominant Negative ◽  
Class I ◽  
Membrane Ruffling ◽  
And Migration ◽  
Phosphoinositide 3 Kinase

Receptor-linked class I phosphoinositide 3-kinases (PI3Ks) induce assembly of signal transduction complexes through protein–protein and protein–lipid interactions that mediate cell proliferation, survival, and migration. Although class II PI3Ks have the potential to make the same phosphoinositides as class I PI3Ks, their precise cellular role is currently unclear. In this report, we demonstrate that class II phosphoinositide 3-kinase C2β (PI3KC2β) associates with the Eps8/Abi1/Sos1 complex and is recruited to the EGF receptor as part of a multiprotein signaling complex also involving Shc and Grb2. Increased expression of PI3KC2β stimulated Rac activity in A-431 epidermoid carcinoma cells, resulting in enhanced membrane ruffling and migration speed of the cells. Conversely, expression of dominant negative PI3KC2β reduced Rac activity, membrane ruffling, and cell migration. Moreover, PI3KC2β-overexpressing cells were protected from anoikis and displayed enhanced proliferation, independently of Rac function. Taken together, these findings suggest that PI3KC2β regulates the migration and survival of human tumor cells by distinct molecular mechanisms.

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