Focal adhesion kinase mediates β-catenin signaling in periodontal ligament cells

Premaraj, Sundaralingam; Souza, Isabela; Premaraj, Thyagaseely Sheela

doi:10.1016/j.bbrc.2013.08.097

Cited by 22 publications

(14 citation statements)

References 26 publications

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“…FAK activation has been linked to b-catenin activation in several ways. The deletion of FAK prevents b-catenin nuclear translocation and gene expression in keratinocytes [65] and similar regulatory roles of FAK in activating b-catenin signaling have been demonstrated in periodontal ligament cells [66], in breast cancer cells [67], in HEK293 and in COS-7 cells [68]. Likely, this regulatory role of FAK is explained by subsequent PI3K activation, which activates b-catenin by inhibiting GSK-3 [67].…”

Section: Role Of B-catenin In Mechanotransductionmentioning

confidence: 58%

β-catenin as a regulator and therapeutic target for asthmatic airway remodeling

Kumawat

Koopmans

Gosens

2014

Expert Opinion on Therapeutic Targets

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The aberrant activation of β-catenin signaling by both WNT-dependent and -independent mechanisms in asthmatic airways plays a key role in remodeling the airways, including cell proliferation, differentiation, tissue repair and extracellular matrix production. These findings are interesting from both a mechanistic and therapeutic perspective, as several drug classes have now been described that target β-catenin signaling directly.

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Section: Role Of B-catenin In Mechanotransductionmentioning

confidence: 58%

β-catenin as a regulator and therapeutic target for asthmatic airway remodeling

Kumawat

Koopmans

Gosens

2014

Expert Opinion on Therapeutic Targets

View full text Add to dashboard Cite

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“…Figure 4 shows higher magnification H&E images and IHC analyses of FAK, TEN and SYN4 expression in multilayered DE DM CSs GelMA constructs cultured in osteogenic media for 24 h and 4 days. FAK is a crucial signaling component that is activated by numerous stimuli and functions as a biosensor or integrator to control cell motility, adhesion and shape [35, 36]. It is a highly phosphorylated tyrosine containing protein that is localized at integrin-enriched cell adhesion sites known as focal contacts.…”

Section: Resultsmentioning

confidence: 99%

Dental cell sheet biomimetic tooth bud model

et al. 2016

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Tissue engineering and regenerative medicine technologies offer promising therapies for both medicine and dentistry. Our long-term goal is to create functional biomimetic tooth buds for eventual tooth replacement in humans. Here, our objective was to create a biomimetic 3D tooth bud model consisting of dental epithelial (DE) – dental mesenchymal (DM) cell sheets (CSs) combined with biomimetic enamel organ and pulp organ layers created using GelMA hydrogels. Pig DE or DM cells seeded on temperature-responsive plates at various cell densities (0.02, 0.114 and 0.228 cells 106/cm2) and cultured for 7, 14 and 21 days were used to generate DE and DM cell sheets, respectively. Dental CSs were combined with GelMA encapsulated DE and DM cell layers to form bioengineered 3D tooth buds. Biomimetic 3D tooth bud constructs were cultured in vitro, or implanted in vivo for 3 weeks. Analyses were performed using micro-CT, H&E staining, polarized light (Pol) microscopy, immunofluorescent (IF) and immunohistochemical (IHC) analyses. H&E, IHC and IF analyses showed that in vitro cultured multilayered DE-DM CSs expressed appropriate tooth marker expression patterns including SHH, BMP2, RUNX2, tenascin and syndecan, which normally direct DE-DM interactions, DM cell condensation, and dental cell differentiation. In vivo implanted 3D tooth bud constructs exhibited mineralized tissue formation of specified size and shape, and SHH, BMP2 and RUNX2and dental cell differentiation marker expression. We propose our biomimetic 3D tooth buds as models to study optimized DE-DM cell interactions leading to functional biomimetic replacement tooth formation.

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“…(D): FAK‐Wnt signaling model—Black dashed arrows show mechanism in DCIS stem cells where active FAK may increase Wnt3a and other Wnt ligands activating Wnt signaling and CSC self‐renewal or may directly activate the β‐Catenin signaling pathway. Published signaling mechanisms and mediators are shown in blue, Wnt3a is upregulated by FAK in Xenopus laevis , FAK signals via Grb2 although Dvl and β‐Catenin or Jnk in HEK293 kidney cells , FAK activates Wnt signaling via PI3K/AKT signaling in skin , lung adenocarcinoma , periodontal ligament cells , and breast cancer cell lines . Fz—Frizzled receptor, β‐Cat—β‐Catenin, Jnk—c‐Jun N‐terminal kinase, Grb‐2—Growth factor receptor‐bound protein 2, Dvl—Dishevelled.…”

Section: Resultsmentioning

confidence: 99%

Focal Adhesion Kinase and Wnt Signaling Regulate Human Ductal Carcinoma In Situ Stem Cell Activity and Response to Radiotherapy

et al. 2015

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Cancer stem cells (CSCs) can avoid or efficiently repair DNA damage from radio and chemotherapy, which suggests they play a role in disease recurrence. Twenty percentage of patients treated with surgery and radiotherapy for ductal carcinoma in situ (DCIS) of the breast recur and our previous data show that high grade DCIS have increased numbers of CSCs. Here, we investigate the role of focal adhesion kinase (FAK) and Wnt pathways in DCIS stem cells and their capacity to survive irradiation. Using DCIS cell lines and patient samples, we demonstrate that CSC-enriched populations are relatively radioresistant and possess high FAK activity. Immunohistochemical studies of active FAK in DCIS tissue show high expression was associated with a shorter median time to recurrence. Treatment with a FAK inhibitor or FAK siRNA in nonadherent and three-dimensional matrigel culture reduced mammosphere formation, and potentiated the effect of 2 Gy irradiation. Moreover, inhibition of FAK in vitro and in vivo decreased selfrenewal capacity, levels of Wnt3a and B-Catenin revealing a novel FAK-Wnt axis regulating DCIS stem cell activity. Overall, these data establish that the FAK-Wnt axis is a promising target to eradicate self-renewal capacity and progression of human breast cancers. STEM CELLS

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Focal adhesion kinase mediates β-catenin signaling in periodontal ligament cells

Cited by 22 publications

References 26 publications

β-catenin as a regulator and therapeutic target for asthmatic airway remodeling

β-catenin as a regulator and therapeutic target for asthmatic airway remodeling

Dental cell sheet biomimetic tooth bud model

Focal Adhesion Kinase and Wnt Signaling Regulate Human Ductal Carcinoma In Situ Stem Cell Activity and Response to Radiotherapy

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