Advances on the roles of tenascin-C in cancer

Yılmaz, Alev; Loustau, Thomas; Salomé, Nathalie; Surendran, Suchithra Poilil; Li, Chengbei; Tucker, Richard P.; Izzi, Valerio; Lamba, Rijuta; Koch, Manuel; Orend, Gertraud

doi:10.1242/jcs.260244

Cited by 31 publications

(20 citation statements)

References 118 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additional CSEs have been reported for FN1 and TNC. 28 , 30 While we excluded the extradomain A of FN1 as an CSE due to expression in several normal tissues ( Supplementary Fig 6A ), we identified additional CSEs for TNC, which have been reported in adult cancer, 30 including the CSE that encode the D domain of TNC ( Supplementary Fig 6B ).…”

Section: Discussionmentioning

confidence: 86%

“…The identified FN1 AS target encodes the alternatively spliced extra domain B of FN1 (EDB) 29 which is highly expressed in all solid and brain tumor types except RB, with the highest prevalence in OS, EWS, RMS, WT, MEL, HGG and EPN ( Extended Data Fig 1 ). TNC encodes an extracellular matrix protein that plays a role during normal development, including neural migration, as well as tumorigenesis 30 , 31 . The TNC AS target encodes the alternatively spliced C domain of TNC 32 with high expression detected at high prevalence in HGG, EPN, OS and MEL ( Extended Data Fig 1 ).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Discovery of immunotherapy targets for pediatric solid and brain tumors by exon-level expression

Shaw,

Wagner,

Tian

et al. 2024

Preprint

View full text Add to dashboard Cite

Immunotherapy with CAR T cells for pediatric solid and brain tumors is constrained by available targetable antigens. Cancer-specific exons (CSE) present a promising reservoir of targets; however, these have not been explored and validated systematically in a pan-cancer fashion. To identify CSE targets, we analyzed 1,532 RNA-seq datasets from 16 types of pediatric solid and brain tumors for comparison with normal tissues using a newly developed workflow. We found 2,933 exons in 157 genes encoding proteins of the surfaceome or matrisome with high cancer specificity either at the gene (n=148) or the alternatively spliced (AS) isoform (n=9) level. Expression of selected AS targets, including the EDB domain of FN1 (EDB), and gene targets, such as COL11A1, were validated in pediatric PDX tumors. We generated CAR T cells specific to EDB or COL11A1 and demonstrated that COL11A1-CAR T-cells have potent antitumor activity. The full target list, explorable via an interactive web portal (https://cseminer.stjude.org/), provides a rich resource for developing immunotherapy of pediatric solid and brain tumors using gene or AS targets with high expression specificity in cancer.

show abstract

Section: Discussionmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Discovery of immunotherapy targets for pediatric solid and brain tumors by exon-level expression

Shaw,

Wagner,

Tian

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Dependent on the individual splicing pattern, oncfTn-C is able to develop various effects in relation to tumor development and progression [139]. It is well known that oncfTn-C is able to modulate tumor cell behavior and inflammatory reaction in a tumor-typedependent manner [140]. There are also several reports on the tumor biological, diagnostic, and prognostic relevance of oncfTn-C in OSCCs [68,[141][142][143].…”

Section: Laminin γ2 Interacts With Oncofetal Fibronectin and Tenascin-cmentioning

confidence: 99%

Invasion-Associated Reorganization of Laminin 332 in Oral Squamous Cell Carcinomas: The Role of the Laminin γ2 Chain in Tumor Biology, Diagnosis, and Therapy

Berndt

Gaßler

Franz

2022

Cancers

View full text Add to dashboard Cite

Invasion of the connective tissue by carcinoma cells is accompanied by disintegration and reorganization of the hemidesmosomes, which connect the basement membrane to the basal epithelial cells. In terms of mediating the basement membrane, i.e., basal cell interactions, the heterotrimeric laminin 332 is the most important bridging molecule. Due to this distinct function, laminin 332, especially its gamma 2 chain, came into the focus of cancer research. Specific de novo synthesis and deposition patterns of laminin 332 are evident upon development and progression of oral squamous cell carcinomas (OSCCs). Loss from the basement membrane, cytoplasmic accumulation, and extracellular deposition are associated with crucial processes such as stromal activation and immune response, epithelial to mesenchymal transition, and tumor cell budding. In networks with components of the tumor microenvironment, altered expression of laminin 332 chains, proteolytic processing, and interaction with integrin receptors seem to promote cancer cell migration. Indeed, reorganization patterns are shown to have a high diagnostic and prognostic value. Here, we summarize the current knowledge on laminin 332 reorganization in OSCCs with special focus on its gamma 2 chain and provide, based on the current literature, evidence on its promising role as a grading and monitoring parameter and as a potential therapeutic target.

show abstract

“…By virtue of its targets, TG2 is an important stabilizer of both the early and more mature wound healing matrix, while LOX was reported to be mostly active after full assembly of the collagen matrix at later stages of tissue maturation (22). Both TNC and TG2 are up-regulated in regions of mechanical stress (34,35), as well as during embryonic development, wound healing, and in fibrotic or neoplastic pathologies (36)(37)(38)(39). Like TNC (40), TG2 is a known myofibroblast activator (38).…”

Section: Introductionmentioning

confidence: 99%

How the mechanobiology orchestrates the iterative and reciprocal ECM-cell cross-talk that drives microtissue growth

et al. 2023

View full text Add to dashboard Cite

Controlled tissue growth is essential for multicellular life and requires tight spatiotemporal control over cell proliferation and differentiation until reaching homeostasis. As cells synthesize and remodel extracellular matrix, tissue growth processes can only be understood if the reciprocal feedback between cells and their environment is revealed. Using de novo–grown microtissues, we identified crucial actors of the mechanoregulated events, which iteratively orchestrate a sharp transition from tissue growth to maturation, requiring a myofibroblast-to-fibroblast transition. Cellular decision-making occurs when fibronectin fiber tension switches from highly stretched to relaxed, and it requires the transiently up-regulated appearance of tenascin-C and tissue transglutaminase, matrix metalloprotease activity, as well as a switch from α5β1 to α2β1 integrin engagement and epidermal growth factor receptor signaling. As myofibroblasts are associated with wound healing and inflammatory or fibrotic diseases, crucial knowledge needed to advance regenerative strategies or to counter fibrosis and cancer progression has been gained.

show abstract

Advances on the roles of tenascin-C in cancer

Cited by 31 publications

References 118 publications

Discovery of immunotherapy targets for pediatric solid and brain tumors by exon-level expression

Discovery of immunotherapy targets for pediatric solid and brain tumors by exon-level expression

Invasion-Associated Reorganization of Laminin 332 in Oral Squamous Cell Carcinomas: The Role of the Laminin γ2 Chain in Tumor Biology, Diagnosis, and Therapy

How the mechanobiology orchestrates the iterative and reciprocal ECM-cell cross-talk that drives microtissue growth

Contact Info

Product

Resources

About