scholarly journals A ZIP6-ZIP10 heteromer controls NCAM1 phosphorylation and integration into focal adhesion complexes during epithelial-to-mesenchymal transition

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Dylan Brethour ◽  
Mohadeseh Mehrabian ◽  
Declan Williams ◽  
Xinzhu Wang ◽  
Farinaz Ghodrati ◽  
...  
Keyword(s):  
Focal Adhesion ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals Artocarpin Targets Focal Adhesion Kinase-Dependent Epithelial to Mesenchymal Transition and Suppresses Migratory-Associated Integrins in Lung Cancer Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 554
Author(s):  
Nongyao Nonpanya ◽  
Kittipong Sanookpan ◽  
Nicharat Sriratanasak ◽  
Chanida Vinayanuwattikun ◽  
Duangdao Wichadakul ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Focal Adhesion Kinase ◽  
Cancer Cells ◽  
Focal Adhesion ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Lung Cancer Cells ◽  
Normal Lung ◽  
Mesenchymal Transition ◽  
Phosphorylated Akt

Focal adhesion kinase (FAK) controls several cancer aggressive potentials of cell movement and dissemination. As epithelial–mesenchymal transition (EMT) and the migratory-associated integrins, known influencers of metastasis, have been found to be linked with FAK activity, this study unraveled the potential pharmacological effect of artocarpin in targeting FAK resulting in the suppression of EMT and migratory behaviors of lung cancer cells. Treatment with artocarpin was applied at concentrations of 0–10 μM, and the results showed non-cytotoxicity in lung cancer cell lines (A549 and H460), normal lung (BEAS-2B) cells and primary metastatic lung cancer cells (ELC12, ELC16, and ELC20). We also found that artocarpin (0–10 µM) had no effect on cell viability, proliferation, and migration in BEAS-2B cells. For metastasis-related approaches, artocarpin significantly inhibited cell migration, invasion, and filopodia formation. Artocarpin also dramatically suppressed anchorage-independent growth, cancer stem cell (CSC) spheroid formation, and viability of CSC-rich spheroids. For molecular targets of artocarpin action, computational molecular docking revealed that artocarpin had the best binding affinity of −8.0 kcal/mol with FAK protein. Consistently, FAK-downstream proteins, namely active Akt (phosphorylated Akt), active mTOR (phosphorylated mTOR), and Cdc42, and EMT marker and transcription factor (N-cadherin, Vimentin, and Slug), were found to be significantly depleted in response to artocarpin treatment. Furthermore, we found the decrease of Caveolin-1 (Cav-1) accompanied by the reduction of integrin-αν and integrin-β3. Taken together, these findings support the anti-metastasis potentials of the compound to be further developed for cancer therapy.

scholarly journals Src- and confinement-dependent FAK activation causes E-cadherin relaxation and β-catenin activity

2018 ◽  
Vol 217 (3) ◽  
pp. 1063-1077 ◽  
Author(s):  
Charlène Gayrard ◽  
Clément Bernaudin ◽  
Théophile Déjardin ◽  
Cynthia Seiler ◽  
Nicolas Borghi
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Epithelial To Mesenchymal Transition ◽  
Nuclear Translocation ◽  
Nuclear Activity ◽  
Kinase Activation ◽  
Mesenchymal Transition ◽  
Cell Substrate ◽  
Quantitative Fluorescence ◽  
E Cadherin

In epithelia, E-cadherin cytoplasmic tail is under cytoskeleton-generated tension via a link that contains β-catenin. A cotranscription factor, β-catenin, is also active in morphogenetic processes associated with epithelial-to-mesenchymal transition. β-Catenin signaling appears mechanically inducible and was proposed to follow phosphorylation-induced β-catenin release from E-cadherin. Evidence for this mechanism is lacking, and whether E-cadherin tension is involved is unknown. To test this, we combined quantitative fluorescence microscopies with genetic and pharmacological perturbations of epithelial-to-mesenchymal transition–induced cells in culture. We showed that β-catenin nuclear activity follows a substantial release from the membrane specific to migrating cells and requires multicellular deconfinement and Src activity. Selective nuclear translocation occurs downstream of focal adhesion kinase activation, which targets E-cadherin tension relaxation through actomyosin remodeling. In contrast, phosphorylations of the cadherin/catenin complex are not substantially required. These data demonstrate that E-cadherin acts as a sensor of intracellular mechanics in a crosstalk with cell-substrate adhesions that target β-catenin signaling.

Focal adhesion kinase mediates TGF-β1-induced renal tubular epithelial-to-mesenchymal transition in vitro

2010 ◽  
Vol 340 (1-2) ◽  
pp. 21-29 ◽  
Author(s):  
Bingqing Deng ◽  
Xiao Yang ◽  
Jianshe Liu ◽  
Fangfang He ◽  
Zhonghua Zhu ◽  
...  
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Renal Tubular ◽  
Tgf Β1

scholarly journals MITF reprograms the extracellular matrix and focal adhesion in melanoma

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ramile Dilshat ◽  
Valerie Fock ◽  
Colin Kenny ◽  
Ilse Gerritsen ◽  
Romain Maurice Jacques Lasseur ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Focal Adhesion ◽  
Epithelial To Mesenchymal Transition ◽  
Residual Disease ◽  
Critical Role ◽  
Melanoma Cells ◽  
Activity Levels ◽  
Mesenchymal Transition ◽  
Expression Of Genes ◽  
Molecular Rheostat

The microphthalmia-associated transcription factor (MITF) is a critical regulator of melanocyte development and differentiation. It also plays an important role in melanoma where it has been described as a molecular rheostat that, depending on activity levels, allows reversible switching between different cellular states. Here, we show that MITF directly represses the expression of genes associated with the extracellular matrix (ECM) and focal adhesion pathways in human melanoma cells as well as of regulators of epithelial-to-mesenchymal transition (EMT) such as CDH2, thus affecting cell morphology and cell-matrix interactions. Importantly, we show that these effects of MITF are reversible, as expected from the rheostat model. The number of focal adhesion points increased upon MITF knockdown, a feature observed in drug-resistant melanomas. Cells lacking MITF are similar to the cells of minimal residual disease observed in both human and zebrafish melanomas. Our results suggest that MITF plays a critical role as a repressor of gene expression and is actively involved in shaping the microenvironment of melanoma cells in a cell-autonomous manner.

scholarly journals MITF reprograms the extracellular matrix and focal adhesion in melanoma

2020 ◽  
Author(s):  
Ramile Dilshat ◽  
Valerie Fock ◽  
Colin Kenny ◽  
Ilse Gerritsen ◽  
Romain Maurice Jacques Lasseur ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Focal Adhesion ◽  
Epithelial To Mesenchymal Transition ◽  
Residual Disease ◽  
Critical Role ◽  
Melanoma Cells ◽  
Activity Levels ◽  
Mesenchymal Transition ◽  
Expression Of Genes ◽  
Molecular Rheostat

AbstractThe microphthalmia associated transcription factor (MITF) is a critical regulator of melanocyte development and differentiation. It also plays an important role in melanoma where it has been described as a molecular rheostat that, depending on activity levels, allows reversible switching between different cellular states. Here we show that MITF directly represses the expression of genes associated with the extracellular matrix (ECM) and focal adhesion pathways in human melanoma cells as well as of regulators of epithelial to mesenchymal transition (EMT) such as CDH2, thus affecting cell morphology and cell-matrix interactions. Importantly, we show that these effects of MITF are reversible, as expected from the rheostat model. The number of focal adhesion points increased upon MITF knockdown, a feature observed in drug resistant melanomas. Cells lacking MITF are similar to the cells of minimal residual disease observed in both human and zebrafish melanomas. Our results suggest that MITF plays a critical role as a repressor of gene expression and is actively involved in shaping the microenvironment of melanoma cells in a cell-autonomous manner.

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