Suppressing the formation of lipid raft‐associated Rac1/PI3K/Akt signaling complexes by curcumin inhibits SDF‐1α‐induced invasion of human esophageal carcinoma cells

Lin, Meng Liang; Lu, Yao; Chen, Hung Yi; Lee, Chuan Chun; Chung, Jing Gung; Chen, Shih Shun

doi:10.1002/mc.21984

Cited by 50 publications

(44 citation statements)

References 69 publications

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“…We show that MT1‐MMP stimulates cell invasion through the recruitment and activation of its effector MMP2. Furthermore, while previous studies have reported activation of MMP2 by RAC1 (Binker et al., ; Lin et al., ), here we demonstrate, for the first time, that MT1‐MMP promotes melanoma cell motility by activating MMP2, which in turn triggers RAC1 leading to an MT1‐MMP/MMP2/RAC1 signaling cascade that controls melanoma cell dissemination.…”

Section: Discussionsupporting

confidence: 69%

“…We show that MT1-MMP stimulates cell invasion through the recruitment and activation of its effector MMP2. Furthermore, while previous studies have reported activation of MMP2 by RAC1 (Binker et al, 2010;Lin et al, 2012), here we demonstrate, for the first time, that MT1-MMP promotes melanoma cell motility by activating MMP2, which in turn triggers RAC1 leading to an MT1-MMP/MMP2/RAC1 signaling cascade that controls melanoma cell dissemination. Interestingly, a recent study by Scott et al (2011) showed that primary melanomas express genes that are correlated with metastatic potential and that these metastasis drivers can be predictive of patient outcome.…”

Section: Discussionsupporting

confidence: 63%

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MT1‐MMP modulates melanoma cell dissemination and metastasis through activation of MMP2 and RAC1

Shaverdashvili

Wong

et al. 2014

Pigment Cell Melanoma Res

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Metastatic melanoma remains the deadliest of all skin cancers with a survival rate at five years of less than 15%. MT1-MMP is a membrane-associated matrix metalloproteinase that controls pericellular proteolysis and is an important, invasion-promoting, pro-tumorigenic MMP in cancer. We show that deregulation of MT1-MMP expression happens as early as the transition from nevus to primary melanoma and continues to increase during melanoma progression. Furthermore, MT1-MMP expression is associated with poor melanoma patient outcome, underscoring a pivotal role of MT1-MMP in melanoma pathogenesis. We demonstrate that MT1-MMP is directly required for melanoma cells to metastasize, as cells deprived of MT1-MMP fail to form distant metastasis in an orthotopic mouse melanoma model. We show that MT1-MMP affects cell invasion by activating its target MMP2. Importantly, we demonstrate, for the first time, that activation of MMP2 by MT1-MMP is required to sustain RAC1 activity and promote MT1-MMP-dependent cell motility. These data highlight a novel MT1-MMP/MMP2/RAC1 signaling axis in melanoma that may represent an intriguing molecular target for the treatment of invasive melanoma.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionsupporting

confidence: 63%

MT1‐MMP modulates melanoma cell dissemination and metastasis through activation of MMP2 and RAC1

Shaverdashvili

Wong

et al. 2014

Pigment Cell Melanoma Res

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“…Lipid raft disruption impairs the Akt signaling pathway in epidermal keratinocytes [40]. Suppressing the formation of raft-associated Akt inhibits SDF-1α-induced invasion of esophageal carcinoma cells [41]. In the present study, we demonstrated that SDF-1α-induced platelet aggregation and Akt phosphorylation are inhibited by the raft disrupting agent MβCD.…”

Section: Discussionsupporting

confidence: 56%

SDF-1α/CXCR4 Signaling in Lipid Rafts Induces Platelet Aggregation via PI3 Kinase-Dependent Akt Phosphorylation

et al. 2017

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Stromal cell-derived factor-1α (SDF-1α)-induced platelet aggregation is mediated through its G protein-coupled receptor CXCR4 and phosphatidylinositol 3 kinase (PI3K). Here, we demonstrate that SDF-1α induces phosphorylation of Akt at Thr308 and Ser473 in human platelets. SDF-1α-induced platelet aggregation and Akt phosphorylation are inhibited by pretreatment with the CXCR4 antagonist AMD3100 or the PI3K inhibitor LY294002. SDF-1α also induces the phosphorylation of PDK1 at Ser241 (an upstream activator of Akt), GSK3β at Ser9 (a downstream substrate of Akt), and myosin light chain at Ser19 (a downstream element of the Akt signaling pathway). SDF-1α-induced platelet aggregation is inhibited by pretreatment with the Akt inhibitor MK-2206 in a dose-dependent manner. Furthermore, SDF-1α-induced platelet aggregation and Akt phosphorylation are inhibited by pretreatment with the raft-disrupting agent methyl-β-cyclodextrin. Sucrose density gradient analysis shows that 35% of CXCR4, 93% of the heterotrimeric G proteins Gαi-1, 91% of Gαi-2, 50% of Gβ and 4.0% of PI3Kβ, and 4.5% of Akt2 are localized in the detergent-resistant membrane raft fraction. These findings suggest that SDF-1α/CXCR4 signaling in lipid rafts induces platelet aggregation via PI3K-dependent Akt phosphorylation.

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“…Curcumin prevents human colon cancer, colo-205 cells migration through the inhibition of NFκB/p65 and downregulation of cyclooxygenase-2 and MMP-2 expression [178] . Lin et al [179] reported that curcumin inhibits SDF-1α-induced invasion of human esophageal carcinoma cells by down regulating MMP-2 promoter activity as well as suppressing the formation of lipid raft-associated Rac1/PI3K/Akt signaling complexes. In conclusion, curcumin appears to have a significant potential in the treatment of multiple diseases that are due to oxidative stress.…”

Section: Curcuminmentioning

confidence: 99%

Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants

Verma

Kesh

Ganguly

et al. 2014

WJBC

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teinase (TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK (reversion including cysteinerich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2, -9 and -14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species (ROS) through mitochondrial dysfunction leading to altered protease/ anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is associated with a lower cancer incidence. Evidence indicates that some antioxidants inhibit the growth of malignant cells by inducing apoptosis and inhibiting the activity of MMPs. This review is discussed in six subchapters, as follows. AbstractThe process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases (MMPs). Degradation of extracellular matrix (ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metallopro-

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Suppressing the formation of lipid raft‐associated Rac1/PI3K/Akt signaling complexes by curcumin inhibits SDF‐1α‐induced invasion of human esophageal carcinoma cells

Cited by 50 publications

References 69 publications

MT1‐MMP modulates melanoma cell dissemination and metastasis through activation of MMP2 and RAC1

MT1‐MMP modulates melanoma cell dissemination and metastasis through activation of MMP2 and RAC1

SDF-1α/CXCR4 Signaling in Lipid Rafts Induces Platelet Aggregation via PI3 Kinase-Dependent Akt Phosphorylation

Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants

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