Early adhesion induces interaction of FAK and Fyn in lipid domains and activates raft-dependent Akt signaling in SW480 colon cancer cells

Baillat, Gilbert; Siret, Carole; Delamarre, Estelle; Luis, José

doi:10.1016/j.bbamcr.2008.08.008

Cited by 56 publications

(48 citation statements)

References 38 publications

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“…Resveratrol binding to integrin a V b 3 (8) could account for the activation of ERK1/2 (42). As resveratrol induced a redistribution of the integrin a V b 3 as well as Akt, FAK, Fyn, and Ras proteins in lipid rafts, our data support that these microdomains may function as microcompartments for the assembly of signaling complexes (43). On integrin ligation, Fyn is activated and binds to SHC, via the SH3 domain of Fyn.…”

Section: Discussionsupporting

confidence: 55%

Endocytosis of Resveratrol via Lipid Rafts and Activation of Downstream Signaling Pathways in Cancer Cells

Colin

Limagne²,

Jeanningros³

et al. 2011

Cancer Prevention Research

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trans-Resveratrol has been proposed to prevent tumor growth and to sensitize cancer cells to anticancer agents. Polyphenol entry into the cells has remained poorly understood. Here, we show that [ 3 H]-resveratrol enters colon cancer cells (SW480, SW620, HT29) and leukemia U937 cells through a monensin (5-20 mmol/L) -sensitive process that suggests clathrin-independent endocytosis. Uptake of the molecule can be prevented by methyl-b-cyclodextrin (2-12 mg/mL), nystatin (12 ng/mL), and filipin (1 mg/mL), which all disrupt plasma membrane lipid rafts. Accordingly, radiolabeled resveratrol accumulates in sphingomyelin-and cholesterol-enriched cell fractions. Interestingly, extracellular signalregulated kinases (ERK), c-Jun NH 2 -terminal kinases (JNK), and Akt also accumulate in lipid rafts on resveratrol exposure (IC 50 at 48 h % 30 mmol/L in SW480 and U937 cells). In these rafts also, resveratrol promotes the recruitment, by the integrin a V b 3 (revealed by coimmunoprecipitation with an anti-integrin a V b 3 antibody), of signaling molecules that include the FAK (focal adhesion kinase), Fyn, Grb2, Ras, and SOS proteins. Resveratrol-induced activation of downstream signaling pathways and caspase-dependent apoptosis is prevented by endocytosis inhibitors, lipid raft-disrupting molecules, and the integrin antagonist peptide arginine-glycine-aspartate (500 nmol/L). Altogether, these data show the role played by lipid rafts in resveratrol endocytosis and activation of downstream pathways leading to cell death.

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Section: Discussionsupporting

confidence: 55%

Endocytosis of Resveratrol via Lipid Rafts and Activation of Downstream Signaling Pathways in Cancer Cells

Colin

Limagne²,

Jeanningros³

et al. 2011

Cancer Prevention Research

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“…Within the lipid raft, Fyn phosphorylates FAK at Y861 and Y925, which leads to the reversed translocation of FAK out of the lipid rafts and thereby activation of the PI3K/Akt pathway. In colon cancer cells (SW480), the Fyn-FAK interaction induces a lipid raft-dependent 'short-term' effect (the activation of the PI3K/Akt pathway) and a lipid raft-independent 'long-term' effect (the activation of the MAPK-Erk1/2 pathway) [33]. Both signaling pathways reinforce the adhesion of cancer cells.…”

Section: The Src Family Kinases and Fyn In Cell Matrix Interaction And Camentioning

confidence: 99%

“…Moreover, it plays a crucial role in integrindependent interactions of epithelial tumor cells with the extracellular matrix and is therefore involved in the control of focal adhesion, cell migration and hematogenous dissemination of epithelial cancer cells. Besides soluble growth factors, integrins can be engaged in triggering recruitment of focal adhesion kinases (FAKs) to lipid rafts and interaction there with Fyn [33]. The adhesion signal initially induces an autophosphorylation of the Fyn-FAK complex at Y397, which drives its sorting into lipid rafts.…”

Section: The Src Family Kinases and Fyn In Cell Matrix Interaction And Camentioning

confidence: 99%

Lipid rafts: signaling and sorting platforms of cells and their roles in cancer

Staubach

Hanisch

2011

Expert Review of Proteomics

252

203

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“…The network pathway identified numerous established targets (including the src tyrosine kinase FYN, which is targeted by dasatinib). 39 Other targets were also identified for which therapeutic targets are available, but which have yet to be characterized in the context of colorectal metastases. For example, COL8A1 is a collagen subtype targeted by clostridium collagenase histolyticum.…”

Section: Discussionmentioning

confidence: 99%

Introducing a Novel and Robust Technique for Determining Lymph Node Status in Colorectal Cancer

et al. 2014

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Objective: This study aims to harness the potential of public gene expression repositories, to develop gene expression profiles that could accurately determine nodal status in colorectal cancer. Background: Currently, techniques that determine lymph node positivity (before resection) have poor sensitivity and specificity. The ability to determine lymph node status, based on preoperative biopsies, would greatly assist in planning treatment in colorectal cancer. This is particularly relevant in polypdetected cancers. Methods: Public gene expression repositories were screened for experiments comparing metastatic and nonmetastatic colorectal cancer. A customized graphic user interface was developed to extract genes dysregulated across most identified studies (ie, consensus profiles). The utility of consensus profiles was tested by determining whether classifiers could be derived that determined nodal positivity or negativity. Consensus profiles-derived classifiers were tested on separate Affymetrix-and Illumina-based experiments, and collated outputs were compiled in summary receiver operator curve characteristic format, with area under the curve (AUC) reflecting accuracy. The association between classification and oncologic outcome was determined using an additional, independent data set. Final validation was conducted using the Ingenuity network-linkage environment. Results: Four consensus profiles were generated from which classifiers were derived that accurately determined node positive and negative status (pooled AUC were 0.79 ± 0.04 and 0.8 ± 0.03 for nodal positivity and negativity, respectively). Overall AUC ranged from 0.73 to 0.86, demonstrating high accuracy across consensus profile type, classification technique, and array platform used. As consensus profile enabled classification of nodal status, survival outcomes could be compared for those predicted node negative or positive. Patterns of disease-free and overall survival were identical to those observed for standard histopathologic nodal status. Genes contained within consensus profiles were strongly linked to the metastatic process and included (among others) FYN, WNT5A, COL8A1, BMP, and SMAD family members. Conclusions: Microarray expression data available in public gene expression repositories can be harnessed to generate consensus profiles. The latter are a source of classifiers that have prognostic and predictive properties.

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Early adhesion induces interaction of FAK and Fyn in lipid domains and activates raft-dependent Akt signaling in SW480 colon cancer cells

Cited by 56 publications

References 38 publications

Endocytosis of Resveratrol via Lipid Rafts and Activation of Downstream Signaling Pathways in Cancer Cells

Endocytosis of Resveratrol via Lipid Rafts and Activation of Downstream Signaling Pathways in Cancer Cells

Lipid rafts: signaling and sorting platforms of cells and their roles in cancer

Introducing a Novel and Robust Technique for Determining Lymph Node Status in Colorectal Cancer

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