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.

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 Are We Benign? What Can Wnt Signaling Pathway and Epithelial to Mesenchymal Transition Tell Us about Intracranial Meningioma Progression

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1633
Author(s):  
Anja Bukovac ◽  
Anja Kafka ◽  
Marina Raguž ◽  
Petar Brlek ◽  
Katarina Dragičević ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
Nuclear Translocation ◽  
Active Form ◽  
Wnt Signaling Pathway ◽  
Future Research ◽  
Intracranial Meningioma ◽  
Mesenchymal Transition ◽  
E Cadherin

Epithelial to mesenchymal transition (EMT), which is characterized by the reduced expression of E-cadherin and increased expression of N-cadherin, plays an important role in the tumor invasion and metastasis. Classical Wnt signaling pathway has a tight link with EMT and it has been shown that nuclear translocation of β-catenin can induce EMT. This research has showed that genes that are involved in cadherin switch, CDH1 and CDH2, play a role in meningioma progression. Increased N-cadherin expression in relation to E-cadherin was recorded. In meningioma, transcription factors SNAIL, SLUG, and TWIST1 demonstrated strong expression in relation to E- and N-cadherin. The expression of SNAIL and SLUG was significantly associated with higher grades (p = 0.001), indicating their role in meningioma progression. Higher grades also recorded an increased expression of total β-catenin followed by an increased expression of its active form (p = 0.000). This research brings the results of genetic and protein analyzes of important molecules that are involved in Wnt and EMT signaling pathways and reveals their role in intracranial meningioma. The results of this study offer guidelines and new markers of progression for future research and reveal new molecular targets of therapeutic interventions.

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 Apigenin Inhibits NNK-Induced Focal Adhesion Kinase Activation in Pancreatic Cancer Cells

Pancreas ◽  
2012 ◽  
Vol 41 (8) ◽  
pp. 1306-1315 ◽  
Author(s):  
Hung Pham ◽  
Monica Chen ◽  
Hiroki Takahashi ◽  
Jonathan King ◽  
Howard A. Reber ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Focal Adhesion Kinase ◽  
Cancer Cells ◽  
Focal Adhesion ◽  
Kinase Activation ◽  
Pancreatic Cancer Cells
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