2020
DOI: 10.3390/ijms21165812
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Enforced C-Src Activation Causes Compartmental Dysregulation of PI3K and PTEN Molecules in Lipid Rafts of Tongue Squamous Carcinoma Cells by Attenuating Rac1-Akt-GLUT-1-Mediated Sphingolipid Synthesis

Abstract: Pharmacologic intervention to affect the membrane lipid homeostasis of lipid rafts is a potent therapeutic strategy for cancer. Here we showed that gallic acid (GA) caused the complex formation of inactive Ras-related C3 botulinum toxin substrate 1 (Rac1)-phospho (p)-casein kinase 2 α (CK2α) (Tyr 255) in human tongue squamous carcinoma (TSC) cells, which disturbed the lipid raft membrane-targeting of phosphatidylinositol 3-kinase (PI3K)-Rac1-protein kinase B (Akt) signal molecules by inducing the association o… Show more

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Cited by 6 publications
(4 citation statements)
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“…Usually, the activation of c-Src induces its own translocation outside the DRM, event necessary to exert its functions. In particular, the translocation of the active form of c-Src is promoted by the enrichment of ceramide in DRM [ 58 , 59 ]. In our models, the reduction in ceramide due to the accumulation of GlcCer within PM DRM could sequester the activated c-Src, avoiding its functioning.…”
Section: Discussionmentioning
confidence: 99%
“…Usually, the activation of c-Src induces its own translocation outside the DRM, event necessary to exert its functions. In particular, the translocation of the active form of c-Src is promoted by the enrichment of ceramide in DRM [ 58 , 59 ]. In our models, the reduction in ceramide due to the accumulation of GlcCer within PM DRM could sequester the activated c-Src, avoiding its functioning.…”
Section: Discussionmentioning
confidence: 99%
“…In most types of human cancer cells, active PI3K–Akt signaling acts as a crucial coordinator of glycolytic and lipid metabolism to conduct the metabolic reprogramming of cancer cells by regulating the glucose transporter-1 (GLUT-1)-mediated glucose uptake [ 85 , 86 ]. Recent studies indicate that a declined Akt activity involving in the low rate of glucose uptake to decrease ATP synthesis of NPC cells was achieved through downregulating of GLUT-1 to the lipid raft membranes [ 38 ]. By using shRNA targeting and pharmacological inhibition strategies in which the oxidative stress-induced ASM activity was attenuated, we have demonstrated here that formation of ceramide-enriched lipid raft domains caused perturbation of p110α, Akt, and Rac1 lipid raft compartmentalization and resulted in the loss of their activity.…”
Section: Discussionmentioning
confidence: 99%
“…This assay was performed as previously described [38]. Briefly, vehicle-treated, apigenin-treated, Z-VAD-FMK-treated, or apigenin and Z-VAD-FMK-treated cells (2.5 × 10 5 ) were washed twice in ice-cold PBS and incubated with 0.5 mg/mL of biotinylated annexin V for 30 min at 4 • C. Biotinylated cells were washed twice in ice-cold PBS and treated with 50 mM NH 4 Cl for 10 min at 4 • C to stop the biotinylation reaction.…”
Section: Cell Surface Biotinylationmentioning
confidence: 99%
“…Targeting the signal regulators required for the mitochondria’s metabolic bioenergetics is a promising strategy for cancer therapy [ 7 ]. Although the aberrant activation of PI3K–Rac1–Akt signaling acts as a crucial coordinator of glycolytic and ER–mitochondrial metabolic functions to conduct the metabolic reprogramming of NPC cells by regulating the lipid raft-associated GLUT-1-mediated glucose uptake [ 30 , 54 ], the precise regulator mechanism of PI3K activation remains unclear. Our findings indicate that KRAS colocalizes and complexes with p110α, p85α, and GTP-Rac1 in the lipid rafts of NPC cells.…”
Section: Discussionmentioning
confidence: 99%