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SPP1 activates CD44. 72 / 86
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"Both basal and +4 cardia stem cells express CD44, which are activated by a CD44 ligand, osteopontin (Fig. 5D) (Fu et al., 2020)."
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"Because of the PVN localization of OPN and CD44, and CD44 being a marker of stem like cells, we asked whether activation of CD44 by OPN could induce the stem like phenotype."
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"Osteopontin derived from HSCs can stimulate the activation of NK cells to express CD44 and IFN-γ and increase NK cell degranulation activity [65]."
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"Additionally, OPN induced radiation resistance by activating the CD44 signaling pathway in glioma [58]."
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"We have previously demonstrated that osteopontin mediated engagement of CD44 spliced variant isoforms promotes an extracellular matrix derived survival signal through integrin activation."
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"al. found that the matricellular protein Osteopontin activated CD44 signalling and thereby promoted stem cell-like characteristics, including radio-resistance in tumor cells within the glioma PVN ( Pi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"SPP1-induced CD44 cleavage results in the expression of hypoxia-related gene , therefore maintenance of the cellular vitality might be provided by SPP1 and CD44 interaction in the hypoxic environment of the PDAC tissue.SCGB3A1 is a surfactant protein which reduces the cell surface tension, so the collective cell movement is induced from aggregate surface region to aggregate core region ."
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"More in depth analyses revealed that the EMT and CSC phenotypes were regulated by osteopontin-dependent activation of CD44 and integrins, and subsequent activation of JAK2/STAT3 and focal adhesion kin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Osteopontin modulates CD44 dependent chemotaxis of peritoneal macrophages through G-protein-coupled receptors : evidence of a role for an intracellular form of osteopontin."
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"In this study, we found that osteopontin expressed by tumor cells enhances extramedullary myelopoiesis in a CD44 dependent manner through the Erk1/2-MAPK pathway."
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"In summary, EEOS significantly inhibited cell adhesion and invasion at nontoxic concentrations, attenuated the expression of OPN and CD44 and also OPN activated CD44 in NCI-H460 cells."
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"OPN can activate CD44 by forming a protein complex that could lead to radiation treatment resistance in glioma [70]."
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"More in depth analyses revealed that the EMT and CSC phenotypes were regulated by osteopontin-dependent activation of CD44 and integrins, and subsequent activation of JAK2/STAT3 and focal adhesion kin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Indeed, OPN increases α v β 3 integrin-dependent activity of the RhoA/ROCK pathway and CD44 exposure to the plasma membrane, suggesting that OPN may indirectly stabilize WASp to locally regulate F-act[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Interestingly, the secreted OPN activated HCV replication, infectivity and assembly through binding to alphaVbeta3 and CD44."
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"siRNAs (ON-TARGETplus) targeting CD44 (L-009999-06), OPN (also referred as SPP1) (L-012558-09) and NT (Non targeting Pool) (D-001810-10-05) were purchased from Thermo Fisher Scientific and transfected with Lipofectamine RNAiMAX (Invitrogen) following the standard protocol."
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"The exact role of the osteopontin-mediated activation of CD44 variants in cardiovascular diseases remains poorly explored and the literature is scarce."
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"We suggest that OPN, adhering to the oolemma, triggers intracellular signals via interaction with integrins and/or CD44."
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"For instance, osteopontin (OPN) elevated the stem cell-like properties and radiation resistance by activating CD44 in adjacent glioma cells [24]."
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"These differential effects of OPN on cardiac myocyte apoptosis under different pathologies may include different neurohormonal response under diverse pathological conditions, cell-type/s involved in the expression of OPN, receptor/s (integrins or CD44) stimulated by OPN and/or differential post-translational modifications of OPN, including phosphorylation and glycosylation."
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"Choi et al. [53] further revealed that TM4SF4 overexpression in A549 cells could increase OPN secretion, which then activated CD44 or integrin signaling, thus maintaining EMT-associated CSC properties."
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"Blocking of CD44 receptor by specific blocking or neutralising antibody or inhibition of the interaction between OPN and CD44 by synthetic small peptide could be useful for suppressing OPN induced CD44 mediated tumour promotion [18]."
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"Tajima et al. demonstrated that OPN mediated the binding of CD44 with hyaluronate (HA), a glycosaminoglycan ubiquitously distributed in the ECM, found to upregulate drug resistance in cancer cells; th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Furthermore, expression of OPN promotes macrophage activation viabinding of CD44, induces a scavenger function and acts against acute tissue destruction."
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"However, OPN is considered to cause tumor progression by affecting the receptors of different integrin and CD44 [ 11 ]."
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"Osteopontin increases hepatocellular carcinoma cell growth in a CD44 dependant manner."
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"In addition to CD44, OPN can mediate proinflammatory or anti-inflammatory phenotypes of immune cells through other receptors on the surface of T cells."
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"Acting through integrin alpha (v) beta (3) and CD44 receptors, OPN can promote chemoattraction and pro inflammatory cytokine expression by macrophages."
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"These studies indicate, therefore, that the level of cell surface CD44 is critical for GPCR mediated chemotaxis by peritoneal macrophages and suggest that a novel intracellular form of OPN may modulate CD44 activities involved in these processes."
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"These results suggest that the OPN secreted by microglia promoted the proliferation of NPCs.Receptors for OPN include CD44 variant 6 (CD44v6), integrin αvβ3, and α5β1."
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"Our observations suggest that OPN/SPP1 could promote stemness signature in PC cells by regulating the CD44-mediated stem cell markers NANOG, KLF4, BMI-1, and ABCG2."
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"OPN significantly increases HCV replication in EpCAM + / CD44 + CSCs."
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"The demonstration in vitro that HA and osteopontin mediated activation of CD44 receptors underpins the synthesis and secretion of cytokines suggests that this receptor may also contribute to the incre[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"OPN mediated CD44 engagement can prevent cell death by activation of the phosphatidylinositol 3-kinase/Akt signaling axis and by inhibition of Fas induced signals [XREF_BIBR, XREF_BIBR]."
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"For example, osteopontin induces CD44 dependent chemotaxis and down-modulates anti-inflammatory IL-10 secretion through interactions with CD44, and is hypothesized as an activator of the CD44 variant survival signal in lymphocytes by the extracellular matrix of the gut mucosa Intriguingly, CD44v7, a principal CD44 isoform sufficient for osteopontin binding, is the isoform present in our Gottron 's papules."
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"Activation of the phosphatidyl-inositol-3 kinase (PI3K)/Akt signalling cascade occurs downstream of either HA or OPN induced activation of CD44 receptors [55,67–69] ."
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"In our study, Rho GTPases gene expression is upregulated by OPN adhesion and the inhibition of adhesion by individually blocking CD44 or β1 containing integrins downregulated Rho GTPases expression.En[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The CD44-dependent spread of tumor cells is mediated by its cytokine ligand osteopontin."
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"OPN mediated increase of MMP-9 and CD44 in prostate cancer cells paired with the fact that highly tumorigenic cells often overexpress OPN provides insight to the observed increase in motility and invasiveness of metastatic cells."
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"Osteopontin, which is derived from the perivascular niche, promotes GSCs phenotype by activating CD44, one of the CSC markers."
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"In detail, we demonstrated that OPN could induce EMT in epithelial cells and CD44/ p-FAK pathway played a key role in this process both in vivo and in vitro."
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"In a recent study, it was shown that osteopontin, possibly derived from astrocytes in the PVN, supports CD44 + glioma stem cells leading to enhanced tumor outgrowth and radiation resistance."
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"These results indicated that OPN increases HCV replication in EpCAM + / CD44 + CSCs through the OPN-CD44 axis."
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"According to research, osteopontin activates CD44 in nearby glioma cells, maintaining the “stem” characteristics and promoting radiation resistance [ 70 ]."
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"Furthermore, osteopontin derived from perivascular niche promotes glioma stem cell-like phenotype by activating CD44, one of the CSC markers."
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"Previous studies found that OPN modulates cell migration, EMT, ECM-invasion and stemness maintaining of tumor cell via binding integrins and CD44 or activating NF-Kb, MEK and MAPK, PI3K and Akt, and FAK pathways XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR."
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"OPN promotes CD44-mediated effects on SCJ epithelium."
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"OPN has been known to bind and activate both integrin and CD44 [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"In this glioma model, the stemness was mediated by the OPN-activated CD44 signaling via the γ-secretase-regulated intracellular domain of CD44."
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"Western blotting revealed that EEOS effectively attenuated the expression of OPN and CD44 and also OPN activated CD44 at nontoxic concentrations in NCI-H460 cells."
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"It has been reported, that through binding to cell surface receptor CD44, perivascular niche-derived OPN promotes the stemness and tumorigenicity of cancer cells via cleavage and translocation of the C-terminal intracellular domain (ICD) of CD44 into the nucleus ."
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"In summary, EEOS significantly inhibited cell adhesion and invasion at nontoxic concentrations, attenuated the expression of OPN and CD44 and also OPN activated CD44 in NCI-H460 cells."
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"In line with this, exogenous HA application increased calcium deposition in pig bone marrow stromal cells [XREF_BIBR], and osteopontin expression was enhanced during bone formation in mouse [XREF_BIBR], indicating the possible involvement of CD44 in bone development."
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"According to research, osteopontin activates CD44 in nearby glioma cells, maintaining the “stem” characteristics and promoting radiation resistance [ 70 ]."
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"We find that, although OPN upregulates plasma membrane total CD44 protein in a concentration- and time-dependent-fashion."
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"Mechanistically, on target cells OPN mediates intracellular communication via integrins and CD44 cell surface adhesion receptors."
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"5 nM OPN increases CD44 protein half-life from 105 ± 11 to 278 ± 15 min ( P < 0.03)."
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"Available data suggest that OPN can activate CD44-mediated pathways to promote cell survival, chemotaxis, homing and adhesion, each potentially enhancing metastatic behavior."
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"29 OPN was also found to increase collagen‐I synthesis via integrin‐CD44 and AKT signaling."
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"This finding indicates the importance of OPN as a cell autonomous growth factor for mesothelioma cells, apparently more relevant than the host derived OPN.Subsequent experiments aimed to provide a proof of principle that pharmacological inhibition of OPN signaling, by targeting the receptor CD44, could indeed decrease mesothelioma cell growth in vivo."
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"CD44 and OPN were found to colocalize in the perivascular niche (where stem-like glioma cells reside), so the question of whether OPN activated CD44 to cause a stem-like phenotype was asked."
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"In our study, in addition to CD44, the expression of OPN increased in H1299-R5 cells."
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"OPN, as the main organic component of the stone matrix, promotes the adhesion of CaOx crystals to surface of tubular cells via binding to its receptor CD44 (30)."
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"OPN can activate CD44 by forming a protein complex that could lead to radiation treatment resistance in glioma [ xref ]."
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"Therefore, we investigated whether OPN triggers AKT activity in neurospheres derived from GBM30 and GBM1600 (both CD44 high), as well as GBM157 (CD44 low) (XREF_FIG, upper left panel)."
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"OPN increases tumor angiogenesis by inducing CD44 receptor and αvβ3 integrin to activate PI3K/Akt, regulate NF-κB/dependent epithelial mesenchymal transition (EMT) signaling, and regulate HIF1α dependent VEGF expression."
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"In addition, OPN selectively induces CD44 dependent chemotaxis, the latter of which contributes to tumor cell migration and invasion."
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"Interestingly, splenic CD44 + T cell survival was not increased by the addition of osteopontin in vitro, which suggests that osteopontin may not affect all T cells expressing CD44."
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"Western blotting revealed that EEOS effectively attenuated the expression of OPN and CD44 and also OPN activated CD44 at nontoxic concentrations in NCI-H460 cells."
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"Regarding the mechanisms involved, OPN activates CD44 and integrins in a para- or autocrine manner and induces PI3K/Akt and mitogen-activated protein kinase (MAPK) signaling ( xref )."
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"Because of the PVN localization of OPN and CD44, and CD44 being a marker of stem-like cells, we asked whether activation of CD44 by OPN could induce the stem-like phenotype."
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"The heightened expression of SPP1 in the EMT-subtype was found to recruit fibroblasts and induce their activation into FAP fibroblasts through binding to CD44."
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