Tenascin-C Promotes Tumor Cell Migration and Metastasis through Integrin α9β1–Mediated YAP Inhibition

Sun, Zhen; Schwenzer, Anja; Rupp, Tristan; Murdamoothoo, Devadarssen; Vegliante, Rolando; Lefèbvre, Olivier; Klein, Albrecht; Hussenet, Thomas; Orend, Gertraud

doi:10.1158/0008-5472.can-17-1597

Cited by 85 publications

(82 citation statements)

References 45 publications

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“…Coley and colleagues injected live and killed streptococci to treat patients afflicted with soft tissue and bone tumors with relative success (Decker et al , ). Interestingly, we now know that osteosarcoma cells express cFn isoforms that contain EDA and/or EDB, as well as TnC (Kilian et al , ; ; Sun et al , ). Here we used the osteosarcoma Saos‐2 cells to produce model matrices, containing those FnIII targets and showed that Scl1 promotes GAS colonization and biofilm formation on Saos‐2‐derived matrices.…”

Section: Discussionmentioning

confidence: 99%

Adaptation of the group A Streptococcus adhesin Scl1 to bind fibronectin type III repeats within wound‐associated extracellular matrix: implications for cancer therapy

McNitt

Choi

Allen

et al. 2019

Molecular Microbiology

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Summary The human‐adapted pathogen group A Streptococcus (GAS) utilizes wounds as portals of entry into host tissue, wherein surface adhesins interact with the extracellular matrix, enabling bacterial colonization. The streptococcal collagen‐like protein 1 (Scl1) is a major adhesin of GAS that selectively binds to two fibronectin type III (FnIII) repeats within cellular fibronectin, specifically the alternatively spliced extra domains A and B, and the FnIII repeats within tenascin‐C. Binding to FnIII repeats was mediated through conserved structural determinants present within the Scl1 globular domain and facilitated GAS adherence and biofilm formation. Isoforms of cellular fibronectin that contain extra domains A and B, as well as tenascin‐C, are present for several days in the wound extracellular matrix. Scl1‐FnIII binding is therefore an example of GAS adaptation to the host's wound environment. Similarly, cellular fibronectin isoforms and tenascin‐C are present in the tumor microenvironment. Consistent with this, FnIII repeats mediate GAS attachment to and enhancement of biofilm formation on matrices deposited by cancer‐associated fibroblasts and osteosarcoma cells. These data collectively support the premise for utilization of the Scl1‐FnIII interaction as a novel method of anti‐neoplastic targeting in the tumor microenvironment.

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Section: Discussionmentioning

confidence: 99%

Adaptation of the group A Streptococcus adhesin Scl1 to bind fibronectin type III repeats within wound‐associated extracellular matrix: implications for cancer therapy

McNitt

Choi

Allen

et al. 2019

Molecular Microbiology

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“…Furthermore, TNC expression in Ewing sarcoma increases upon microenvironmental stress (hypoxia or nutrient deprivation) [213]. Interestingly, while in osteosarcoma, TNC binding to α9β1 integrin promoted metastasis by repressing YAP nuclear translocation and target gene activation [214], TNC binding to α5β1 integrin in Ewing sarcoma promoted metastasis by activating YAP [207], potentially through activating tyrosine phosphorylation by SRC kinase [213].…”

Section: Yap/taz In Ewing Sarcomamentioning

confidence: 99%

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

Kovar

Bierbaumer

Radic-Sarikas

2020

Cells

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YAP and TAZ are intracellular messengers communicating multiple interacting extracellular biophysical and biochemical cues to the transcription apparatus in the nucleus and back to the cell/tissue microenvironment interface through the regulation of cytoskeletal and extracellular matrix components. Their activity is negatively and positively controlled by multiple phosphorylation events. Phenotypically, they serve an important role in cellular plasticity and lineage determination during development. As they regulate self-renewal, proliferation, migration, invasion and differentiation of stem cells, perturbed expression of YAP/TAZ signaling components play important roles in tumorigenesis and metastasis. Despite their high structural similarity, YAP and TAZ are functionally not identical and may play distinct cell type and differentiation stage-specific roles mediated by a diversity of downstream effectors and upstream regulatory molecules. However, YAP and TAZ are frequently looked at as functionally redundant and are not sufficiently discriminated in the scientific literature. As the extracellular matrix composition and mechanosignaling are of particular relevance in bone formation during embryogenesis, post-natal bone elongation and bone regeneration, YAP/TAZ are believed to have critical functions in these processes. Depending on the differentiation stage of mesenchymal stem cells during endochondral bone development, YAP and TAZ serve distinct roles, which are also reflected in bone tumors arising from the mesenchymal lineage at different developmental stages. Efforts to clinically translate the wealth of available knowledge of the pathway for cancer diagnostic and therapeutic purposes focus mainly on YAP and TAZ expression and their role as transcriptional co-activators of TEAD transcription factors but rarely consider the expression and activity of pathway modulatory components and other transcriptional partners of YAP and TAZ. As there is a growing body of evidence for YAP and TAZ as potential therapeutic targets in several cancers, we here interrogate the applicability of this concept to bone tumors. To this end, this review aims to summarize our current knowledge of YAP and TAZ in cell plasticity, normal bone development and bone cancer.Cells 2020, 9, 972 2 of 34 co-activators Yes-associated protein 1 (YAP-1, YAP) and its paralogue, the transcriptional co-activator with PDZ-binding motif (TAZ, WWTR1), which are typically controlled on the post-translational level by upstream regulatory signaling pathways in organ development and tissue homeostasis [2,3]. YAP and TAZ were reported to affect self-renewal and lineage commitment of stem cells [4][5][6][7], while hyperactivation of YAP and TAZ have been linked to cancer growth and metastasis in various tumors [8][9][10]. TAZ levels are elevated in approximately 20% of cancers and drive invasion and metastasis [11,12], while YAP is frequently overexpressed or amplified in cancer and was shown to promote resistance to chemotherapy in oncogene-addicted tumors up...

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“…While integrating TN-C, it is possible that POSTN could also serve as a scaffold for BMP-1, LOX-1 and collagen to accelerate collagen crosslinking into migratory tracks during metastasis (172). Mechanistically, track mobility involves TN-C competing for syndecan-4 binding to fibronectin, which blocks integrin α5β1mediated cell adhesion for detachment (139), followed by TN-C promotion of migration through integrin α9β1 following YAP inactivation (209). As previously discussed, TN-C and POSTN can bind multiple ECM proteins (i.e.…”

Section: Mcp Influence On the Metastatic Nichementioning

confidence: 99%

The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment

et al. 2020

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The extracellular matrix (ECM) surrounding cells is indispensable for regulating their behavior. The dynamics of ECM signaling are tightly controlled throughout growth and development. During tissue remodeling, matricellular proteins (MCPs) are secreted into the ECM. These factors do not serve classical structural roles, but rather regulate matrix proteins and cell-matrix interactions to influence normal cellular functions. In the tumor microenvironment, it is becoming increasingly clear that aberrantly expressed MCPs can support multiple hallmarks of carcinogenesis by interacting with various cellular components that are coupled to an array of downstream signals. Moreover, MCPs also reorganize the biomechanical properties of the ECM to accommodate metastasis and tumor colonization. This realization is stimulating new research on MCPs as reliable and accessible biomarkers in cancer, as well as effective and selective therapeutic targets. Research.

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Tenascin-C Promotes Tumor Cell Migration and Metastasis through Integrin α9β1–Mediated YAP Inhibition

Cited by 85 publications

References 45 publications

Adaptation of the group A Streptococcus adhesin Scl1 to bind fibronectin type III repeats within wound‐associated extracellular matrix: implications for cancer therapy

Adaptation of the group A Streptococcus adhesin Scl1 to bind fibronectin type III repeats within wound‐associated extracellular matrix: implications for cancer therapy

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment

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