Hippo Signaling-Mediated Mechanotransduction in Cell Movement and Cancer Metastasis

Chang, Yu Chiuan; Wu, Jhen Wei; Wang, Chueh Wen; Jang, Anna C.C.

doi:10.3389/fmolb.2019.00157

Cited by 65 publications

(60 citation statements)

References 56 publications

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“…Hippo signalling is also required in many other processes, such as epithelial to mesenchymal transition and cellular polarity. 14,20,[62][63][64][65][66] The Hippo pathway was initially characterized in Drosophila utilizing larval wing and eye imaginal disc epithelium. 67 The core of this path- 2A).…”

Section: Hippo Signallingmentioning

confidence: 99%

“…61 The Hippo pathway is highly conserved and best known for regulating tissue and organ size. Hippo signalling is also required in many other processes, such as epithelial to mesenchymal transition and cellular polarity 14,20,62‐66 . The Hippo pathway was initially characterized in Drosophila utilizing larval wing and eye imaginal disc epithelium 67 .…”

Section: Ajuba Maintains Adult Epidermal Homeostasismentioning

confidence: 99%

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AJUBA: A regulator of epidermal homeostasis and cancer

Schleicher

Schramek

2021

Experimental Dermatology

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The epidermis, outermost layer of the skin, is constantly renewing itself through proliferative and differentiation processes. These processes are vital to maintain proper epidermal integrity during skin development and homeostasis and for preventing skin diseases and cancers. The biological mechanisms that permit this balancing act are vast, where individual pathway regulators are known, but the exact regulatory control and cross-talk between simultaneously turning one biological pathway on and an opposing one off remain elusive. This review explores the diverse roles the scaffolding protein AJUBA plays during epidermal homeostasis and cancer. Initially identified for its role in promoting meiotic progression in oocytes through Grb2 and MAP kinase activity, AJUBA also maintains cytoskeletal tension permitting epidermal tissue development and responds to retinoic acid committing cells to initiate development of surface epidermal layer. AJUBA regulates proliferation of skin stem cells through Hippo and Wnt signalling and encourages mitotic commitment through Aurora-A, Aurora-B and CDK1. In addition, AJUBA also induces epidermal differentiation to maintain appropriate epidermal thickness and barrier function by activating Notch signalling and stabilizing catenins and actin during cellular remodelling. AJUBA also plays an imperative context-dependent tumor-promoting and tumor-suppressive role within epithelial cancers. AJUBA's abundant roles within the epidermis signify its importance as a molecular switchboard, vetting multiple signalling pathways to control epidermal biology.

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Section: Hippo Signallingmentioning

confidence: 99%

Section: Ajuba Maintains Adult Epidermal Homeostasismentioning

confidence: 99%

AJUBA: A regulator of epidermal homeostasis and cancer

Schleicher

Schramek

2021

Experimental Dermatology

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“…Cell-cell adhesion and the adhesion of cells to the extracellular matrix (ECM), mediated by the specific binding of receptors and ligands anchored to the apposing surfaces, governs numerous biological processes such as signal transduction, immune responses, cell locomotion, tissue formation, as well as cancer invasion and metastasis (Weikl and Lipowsky, 2004;Krobath et al, 2009;van der Merwe and Dushek, 2011;Benham-Pyle et al, 2015;Chang et al, 2020;Romani et al, 2021). In cell-cell adhesion, both receptors and ligands are laterally mobile, whereas in cell-ECM adhesion, mobile receptors on the cell membranes often bind immobile ligands presented on the apposing surface (Sackmann and Smith, 2014).…”

Section: Introductionmentioning

confidence: 99%

Interplay Between Receptor-Ligand Binding and Lipid Domain Formation Depends on the Mobility of Ligands in Cell-Substrate Adhesion

Wang

et al. 2021

Front. Mol. Biosci.

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Cell-cell adhesion and the adhesion of cells to extracellular matrix are mediated by the specific binding of receptors on the cell membrane to their cognate ligands on the opposing surface. The adhesion receptors can exhibit affinity for nanoscale lipid clusters that form in the cell membrane. Experimental studies of such adhesion systems often involve a cell adhering either to a solid surface with immobile ligands or a supported lipid bilayer with mobile ligands. A central question in these cell-substrate adhesions is how the mobility of the ligands physically affects their binding to the adhesion receptors and thereby the behavior of the nanoscale lipid clusters associated with the receptors. Using a statistical mechanical model and Monte Carlo simulations for the adhesion of cells to substrates with ligands, we find that, for mobile ligands, binding to adhesion receptors can promote the formation of mesoscale lipid domains, which in turn enhances the receptor-ligand binding. However, in the case of immobile ligands, the receptor-ligand binding and the tendency for the nanoscale lipid clusters to further coalesce depend on the distribution of the ligands on the substrate. Our findings help to explain why different adhesion experiments for identifying the interplay between receptor-ligand binding and heterogeneities in cell membranes led to contradictory results.

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“…An AMOT-dependent complex, which comprised of AMOT, Pals, Merlin, and Patj, functions upstream of the core Hippo pathway kinases LATS1/2 and MST1/2 [18,19]. Based on the predicted domain structure of SIPA1L3, it possesses an N-terminal PDZ domains, which is predicted to be required for protein-protein interactions.…”

Section: Discussionmentioning

confidence: 99%

“…It formed AMOT-mediated complex, such as AMOT-Pals-Merlin-Patj complex, activating Hippo pathway. In the C-terminal region of AMOT, it composes of the PDZ-binding domain [18][19][20]. Base on SIPA1L3 possessing PDZ domain, we used SIPA1L3 and AMOT antibody for immunoprecipitation, respectively, and the obtained proteins were detected by western blot.…”

Section: Combination Of Sipa1l3 and Amot Inhibits The Hippo Pathwaymentioning

confidence: 99%

Knockdown of SIPA1L3 Inhibits the Proliferation and Invasion of Non–Small Cell Lung Cancer Cells Through the Hippo Pathway

Wang¹,

Han²,

Rong³

et al. 2021

Preprint

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Background: SIPA1L3 is a member of the signal-induced proliferation-associated (SIPA) protein family, only limited data about the SIPA1L3 are currently available in human carcinoma. Our present study provides the expression pattern and function of SIPA1L3 in non-small cell lung cancer (NSCLC).Methods: We performed immunohistochemistry to detect the distribution of SIPA1L3 in NSCLC specimens and analyzed the relationship between SIPA1L3 expression and patients clinicopathological feature. We used small interfering RNA (siRNA) to specifically silence SIPA1L3, then investigated its effect on cell growth and invasion in human lung cancer cell lines. Western blot and immunoprecipitation were performed to show the interaction of SIPA1L3 with the core proteins of Hippo pathway, and the Hippo pathway activity.Results: Immunohistochemical staining showed that SIPA1L3 was cytoplasmic increasing in 147 of 217 cases. High levels of SIPA1L3 expression were associated with poor differentiation and a high tumor node metastasis stage, positive lymph nodal status, and poor prognosis. Downregulation of SIPA1L3 inhibited cell EMT, growth, and invasion. As well as SIPA1L3 inhibited Hippo pathway. SIPA1L3 interacted with AMOT, which inhibited AMOT binding to Pals, then decreased nuclear location of YAP.Conclusions: SIPA1L3 overexpression may be a marker for advanced NSCLC. SIPA1L3 reduction inhibits the proliferative and invasive ability of the lung cancer cells, which involves the Hippo pathway by contacting with AMOT.

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Hippo Signaling-Mediated Mechanotransduction in Cell Movement and Cancer Metastasis

Cited by 65 publications

References 56 publications

AJUBA: A regulator of epidermal homeostasis and cancer

AJUBA: A regulator of epidermal homeostasis and cancer

Interplay Between Receptor-Ligand Binding and Lipid Domain Formation Depends on the Mobility of Ligands in Cell-Substrate Adhesion

Knockdown of SIPA1L3 Inhibits the Proliferation and Invasion of Non–Small Cell Lung Cancer Cells Through the Hippo Pathway

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