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TNC

MIM.187380 9q33

Monday 9 January 2006

Tenascin, also known as hexabrachion and cytotactin, is an extracellular matrix protein with a spatially and temporally restricted tissue distribution.

Structure

It is a hexomeric, multidomain protein with disulfide-linked subunits of 190 to 240 kD, originally characterized as ’myotendinous antigen.’

Expression

In the embryo it is present in dense mesenchyme surrounding developing epithelia, in tendon anlagen, and in developing cartilage and bone.

In the adult tenascin remains present in tendons and myotendinous junctions in the perichondrium and periosteum, as well as in smooth muscle.

The tenacin family consist of large multimeric proteins involved in morphogenesis and cell adhesion.

Pathology

- Tumour-associated tenascin-C isoforms promote breast cancer cell invasion and growth by matrix metalloproteinase-dependent and independent mechanisms. (#19405959#)

- Association of invasion-promoting tenascin-C additional domains with breast cancers in young women. (#20678196#)

- TNC is differentially expressed in early and late-stage oral squamous cell carcinoma. (#18234543#)

- Tenascin-C (TNC) expression is known to correlate with malignancy in glioblastoma (GBM), a highly invasive and aggressive brain tumor that shows limited response to conventional therapies. (#19147558#)

  • In these malignant gliomas as well as in GBM cell lines, NOTCH2 protein is strongly expressed.
  • In a GBM tumor tissue microarray, RBPJk protein, a Notch2 cofactor for transcription, was found to be significantly coexpressed with TNC.
  • The TNC gene is transactivated by NOTCH2 in an RBPJk-dependent manner mediated by an RBPJk binding element in the TNC promoter.
  • The transactivation is abrogated by a NOTCH2 mutation. This L1711M mutation resides in the RAM domain, the site of interaction between Notch2 and RBPJk.
  • In addition, transfection of constructs encoding activated NOTCH2 or NOTCH1 increased endogenous TNC expression identifying TNC as a novel Notch target gene.
  • Overexpression of a dominant negative form of the transcriptional coactivator MAML1 or knocking down RBPJk in LN319 cells led to a dramatic decrease in TNC protein levels accompanied by a significant reduction of cell migration.
  • Because addition of purified TNC stimulated glioma cell migration, this represents a mechanism for the invasive properties of glioma cells controlled by Notch signaling and defines a novel oncogenic pathway in gliomagenesis that may be targeted for therapeutic intervention in GBM patients.

- Tenascin C and tenascin XB (TNXB) are possibly involved in tumorigenesis associated with neurofibromatosis type 1. (#17202312#)

- Tenascin-C promotes cell survival by activation of AKT in human chondrosarcoma cell. (#16157221#)

- Tenascin-C and SF/HGF produced by myofibroblasts in vitro provide convergent pro-invasive signals to human colon cancer cells through RhoA and Rac. (#15059978#)

Immunochemistry

- Differential diagnosis of dermatofibroma (fibrous histiocytoma) vs dermatofibrosarcoma protuberans (#11172295#)

- DF DFSP
CD34 25% 80%
FXIIIa 95% 15%
Tenascin in the tumor 80% 80%
Tenascin at the dermal-epidermal junction 100% 0%

- Tenascin C and tenascin XB (TNXB) are possibly involved in tumorigenesis associated with neurofibromatosis type 1. (#17202312#)

See also

- tenascins (TNs)

  • TNXB

References

- Microarray-based identification of tenascin C and tenascin XB, genes possibly involved in tumorigenesis associated with neurofibromatosis type 1. Lévy P, Ripoche H, Laurendeau I, Lazar V, Ortonne N, Parfait B, Leroy K, Wechsler J, Salmon I, Wolkenstein P, Dessen P, Vidaud M, Vidaud D, Bièche I. Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):398-407. PMID: #17202312#