Targeting Focal Adhesion Assembly by Ethoxyfagaronine Prevents Lymphoblastic Cell Adhesion to Fibronectin

Ouchania, F.

doi:10.1155/2012/351674

Cited by 4 publications

(3 citation statements)

References 35 publications

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“…They have also been shown to modulate cell division by facilitating the ILK-dependent orientation of the centrosomes and the organisation of the mitotic spindle [ 123 ], indicating a role in cell proliferation. Targeting the disassembly of focal contacts in combination with cytotoxic drugs could improve therapies for relapse and refractory leukaemia patients [ 124 , 125 , 126 ].…”

Section: Invasive Adhesions Formed By Cells Undergoing Emt In Solid T...mentioning

confidence: 99%

Epithelial Mesenchymal Transition (EMT) and Associated Invasive Adhesions in Solid and Haematological Tumours

Greaves

Calle

2022

Cells

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In solid tumours, cancer cells that undergo epithelial mesenchymal transition (EMT) express characteristic gene expression signatures that promote invasive migration as well as the development of stemness, immunosuppression and drug/radiotherapy resistance, contributing to the formation of currently untreatable metastatic tumours. The cancer traits associated with EMT can be controlled by the signalling nodes at characteristic adhesion sites (focal contacts, invadopodia and microtentacles) where the regulation of cell migration, cell cycle progression and pro-survival signalling converge. In haematological tumours, ample evidence accumulated during the last decade indicates that the development of an EMT-like phenotype is indicative of poor disease prognosis. However, this EMT phenotype has not been directly linked to the assembly of specific forms of adhesions. In the current review we discuss the role of EMT in haematological malignancies and examine its possible link with the progression towards more invasive and aggressive forms of these tumours. We also review the known types of adhesions formed by haematological malignancies and speculate on their possible connection with the EMT phenotype. We postulate that understanding the architecture and regulation of EMT-related adhesions will lead to the discovery of new therapeutic interventions to overcome disease progression and resistance to therapies.

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Section: Invasive Adhesions Formed By Cells Undergoing Emt In Solid T...mentioning

confidence: 99%

Epithelial Mesenchymal Transition (EMT) and Associated Invasive Adhesions in Solid and Haematological Tumours

Greaves

Calle

2022

Cells

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“…Pyk2 regulates AML cell adhesion and enhances AML progression through cross-talking with FMS-like receptor tyrosine kinase 3 (FLT3) and β1 integrin [ 67 ]. Ethoxy fagaronine has anti-adhesive potential and inhibits leukemic cell survival via reducing Pyk2 phosphorylation on Tyr 579, impairing β1 integrin clustering and inhibiting phosphatidylinositol 3-kinase (PI 3-kinase) activity [ 24 ]. Pyk2 acts as an oncogene and participates in maintaining leukemia development.…”

Section: Leukemiamentioning

confidence: 99%

“…Kinase activity of Pyk2 is generally initiated by autophosphorylation of the tyrosine Y402 situated in the FERM-kinase linker [ 21 ]. The phosphorylation sites Tyr402, Tyr579, and Tyr580 are also reported to take part in regulating the growth of tumor cells [ 22 – 24 ]. Pyk2 has the centrally located kinase domain, which may be of potential use in the design of selective kinase inhibitors for targeting cancers [ 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Role of Pyk2 in Human Cancers

Shen

Guo

2018

Med Sci Monit

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Proline-rich tyrosine kinase 2 (Pyk2) plays essential roles in tumorigenesis and tumor progression. Pyk2 serves as a non-receptor tyrosine kinase regulating tumor cell survival, proliferation, migration, invasion, metastasis, and chemo-resistance, and is associated with poor prognosis and shortened survival in various cancer types. Thus, Pyk2 has been traditionally regarded as an oncogene and potential therapeutic target for cancers. However, a few studies have also demonstrated that Pyk2 exerts tumor-suppressive effects in some cancers, and anti-cancer treatment of Pyk2 inhibitors may only achieve marginal benefits in these cancers. Therefore, more detailed knowledge of the contradictory functions of Pyk2 is needed. In this review, we summarized the tissue distribution, expression, interactive molecules of Pyk2 in the signaling pathway, and roles of Pyk2 in cancers, and focused on regulation of the interconnectivity between Pyk2 and its downstream targets. The potential use of inhibitors of Pyk2 and its related pathways in cancer therapy is also discussed.

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Ethoxyfagaronine, a synthetic analogue of fagaronine that inhibits vascular endothelial growth factor-1, as a new anti-angiogeneic agent

et al. 2014

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Angiogenesis plays a pivotal role in tumorigenesis and also contributes to the pathogenesis of hematologic malignancies. A number of plant compounds have shown efficacy in preclinical and clinical studies and some of them possess an anti-angiogenic activity. Our present findings report anti-angiogenic activities of ethoxyfagaronine (etxfag), a synthetic derivative of fagaronine. Once determined the non-cytotoxic concentration of etxfag, we showed that the drug inhibits VEGF-induced angiogenesis in a Matrigel™ plug assay and suppresses ex vivo sprouting from VEGF-treated aortic rings. Each feature leading to neovascularization was then investigated and results demonstrate that etxfag prevents VEGF-induced migration and tube formation in human umbilical vein endothelial cells (HUVEC). Moreover, etxfag also suppresses VEGF-induced VEGFR-2 phosphorylation and inhibits FAK phosphorylation at Y-861 as well as focal adhesion complex turnover. Beside these effects, etxfag modifies MT1-MMP localization at the endothelial cell membrane. Finally, immunoprecipitation assay revealed that etxfag decreases VEGF binding to VEGFR-2. As we previously reported that etxfag is able to prevent leukemic cell invasiveness and adhesion to fibronectin, all together our data collectively support the anti-angiogenic activities of etxfag which could represent an additional approach to current anti-cancer therapies.

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Targeting Focal Adhesion Assembly by Ethoxyfagaronine Prevents Lymphoblastic Cell Adhesion to Fibronectin

Cited by 4 publications

References 35 publications

Epithelial Mesenchymal Transition (EMT) and Associated Invasive Adhesions in Solid and Haematological Tumours

Epithelial Mesenchymal Transition (EMT) and Associated Invasive Adhesions in Solid and Haematological Tumours

Role of Pyk2 in Human Cancers

Ethoxyfagaronine, a synthetic analogue of fagaronine that inhibits vascular endothelial growth factor-1, as a new anti-angiogeneic agent

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