Alternative titles; symbols
HGNC Approved Gene Symbol: TNS3
Cytogenetic location: 7p12.3 Genomic coordinates (GRCh38): 7:47,275,154-47,582,586 (from NCBI)
Using serial analysis of gene expression (SAGE), St. Croix et al. (2000) identified partial cDNAs corresponding to several tumor endothelial markers (TEMs) that displayed elevated expression during tumor angiogenesis. Among the genes they identified was TEM6. Using database searches and 5-prime RACE, Carson-Walter et al. (2001) derived sequences covering the entire TEM6 coding region, which encodes a 261-amino acid protein.
By searching databases for sequences similar to tensin-1 (TNS1; 600076), Cui et al. (2004) identified a full-length tensin-3 cDNA. The deduced 1,445-amino acid protein has a calculated molecular mass of 155.3 kD. Like other tensins, tensin-3 has an N-terminal actin-binding domain and C-terminal SH2 and PTB domains. It also has several potential tyrosine phosphorylation sites. Northern blot analysis detected high expression of an 8-kb transcript in kidney and placenta, with weaker expression in heart, skeletal muscle, spleen, liver, and lung. Western blot analysis revealed a 180-kD tensin-3 protein in human endothelial and epithelial cells and fibroblasts. Immunofluorescence analysis localized tensin-3 to focal adhesions in human lung epithelial cells.
Using RT-PCR, Maeda et al. (2006) found that expression of tensin-3 was high in thyroid, moderate in placenta, and low in other tissues examined.
Cui et al. (2004) found that EGF (131530) induced tyrosine phosphorylation of tensin-3 in human breast carcinoma cells in a time- and dose-dependent manner. Tyrosine phosphorylation of tensin-3 required activation of EGF receptor (EGFR; 131550) and SRC (190090) family kinase activity. Tensin-3 formed a complex with focal adhesion kinase (FAK, or PTK2; 600758) and p130Cas (BCAR1; 602941) in human breast carcinoma cells. Addition of EGF to these cells induced dephosphorylation of FAK and p130Cas, leading to dissociation of the tensin-3/FAK/p130Cas complex and enhanced interaction between tensin-3 and EGFR. Cui et al. (2004) proposed that tensin-3 functions as a platform for disassembly of EGF-related signaling complexes at focal adhesions.
Katz et al. (2007) found that EGF downregulated expression of tensin-3 and concomitantly upregulated expression of CTEN (TNS4; 608385), a tensin family member that lacks the actin-binding domain, in HeLa cells and human breast carcinoma cells. Knockdown of CTEN or tensin-3 impaired or enhanced mammary cell migration, respectively. Furthermore, CTEN displaced tensin-3 from the cytoplasmic tail of integrin beta-1 (ITGB1; 135630), thereby inducing actin fiber disassembly. In invasive breast cancer, CTEN expression correlated with high EGFR and HER2 (ERBB2; 164870) expression and with metastasis to lymph nodes. Moreover, treatment of inflammatory breast cancer patients with an EGFR/HER2 inhibitor significantly downregulated CTEN expression. Katz et al. (2007) concluded that a transcriptional tensin-3-CTEN switch may contribute to metastasis of mammary cancer.
Using sequence-specific differential display, Maeda et al. (2006) found that expression of tensin-3 was downregulated in thyroid tumors compared with normal thyroid tissue.
Stumpf (2022) mapped the TNS3 gene to chromosome 7p12.3 based on an alignment of the TNS3 sequence (GenBank BC137134) with the genomic sequence (GRCh38).
Carson-Walter, E. B., Watkins, D. N., Nanda, A., Vogelstein, B., Kinzler, K. W., St. Croix, B. Cell surface tumor endothelial markers are conserved in mice and humans. Cancer Res. 61: 6649-6655, 2001. [PubMed: 11559528]
Cui, Y., Liao, Y.-C., Lo, S. H. Epidermal growth factor modulates tyrosine phosphorylation of a novel tensin family member, tensin3. Molec. Cancer Res. 2: 225-232, 2004. [PubMed: 15140944]
Katz, M., Amit, I., Citri, A., Shay, T., Carvalho, S., Lavi, S., Milanezi, F., Lyass, L., Amariglio, N., Jacob-Hirsch, J., Ben-Chetrit, N., Tarcic, G., Lindzen, M., Avraham, R., Liao, Y.-C., Trusk, P., Lyass, A., Rechavi, G., Spector, N. L., Lo, S. H., Schmitt, F., Bacus, S. S., Yarden, Y. A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration. Nature Cell Biol. 9: 961-969, 2007. [PubMed: 17643115] [Full Text: https://doi.org/10.1038/ncb1622]
Maeda, I., Takano, T., Yoshida, H., Matsuzuka, F., Amino, N., Miyauchi, A. Tensin3 is a novel thyroid-specific gene. J. Molec. Endocr. 36: R1-R8, 2006. [PubMed: 16461921] [Full Text: https://doi.org/10.1677/jme.1.01913]
St. Croix, B., Rago, C., Velculescu, V., Traverso, G., Romans, K. E., Montgomery, E., Lal, A., Riggins, G. J., Lengauer, C., Vogelstein, B., Kinzler, K. W. Genes expressed in human tumor endothelium. Science 289: 1197-1202, 2000. [PubMed: 10947988] [Full Text: https://doi.org/10.1126/science.289.5482.1197]
Stumpf, A. M. Personal Communication. Baltimore, Md. 01/18/2022.