TMSB10 (thymosin beta 10)

2014-12-01   Xueshan Qiu , Yumei Gu 

Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China

Identity

HGNC
LOCATION
2p11.2
LOCATION
2p11.2
LOCUSID
ALIAS
MIG12,TB10
FUSION GENES

Abstract

TMSB10 (thymosin beta 10) is a member of the beta-thymosin family, which is an actin-sequestering protein involved in cell motility. The expression of TMSB10 is associated with the development of several tissues. In many kind of human cancers, TMSB10 expression is aberrant. TMSB10 may be correlated with tumor cells proliferation, apoptosis, metastasis and angiogenesis, and predict poor prognosis of some tumors.

DNA/RNA

Atlas Image

Description

The cDNA sequence for human TMSB10 is 482 nucleotides long comprising 3 exons. The open reading frame of the coding region is 135 bp.

Proteins

Atlas Image

Description

Protein length (NP_066926.1): 44 amino acids. (madkpdmgeiasfdkaklkktetqekntlptketieqekrseis)
Molecular weight: 4.9 kDa.
TMSB10 is a small G-actin binding protein, and it induces depolymerization of intracellular F-actin pools by sequestering actin monomers.

Expression

TMSB10 is found in human, rat, mouse, cat, and rabbit. TMSB10 is one of the most abundant beta-thymosins.

Localisation

TMSB10 is expressed in cytoplasm.

Function

Overview: TMSB10 is a highly conserved small acid protein. It is present in many tissues and cell types. It can sequester actin monomers and bind to G-actin in a 1:1 complex.

Actin monomer sequestering protein: TMSB10 is one of G-actin binding proteins, being expressed in all mammalian species. It can sequester monomeric actin and inhibit actin polymerization. It participates in the regulation of cancer cell motility (Erickson-Viitanen S et al., 1983; Abiko T et al., 1986; Goodall GJ et al., 1987; McCreary V et al.,1988; Nachmias VT,1993; Yu FX et al.,1993; Yu FX et al.,1994; Huff T et al.,1997; Vassiliadou I,1999; Liu CR et al.,2004; Mu H et al.,2006).

Development: The expression of TMSB10 is associated with the development of several tissues. It is involved in the development of the oral cavity and its annexes and developing salivary gland and kidney. TMSB10 may be have multiple functions in the developmental course from initiation to root formation of the tooth germ.. TMSB10 plays an important role in early neuroembryogenesis. It is present in the developing nervous, and has a specific physiological function during cerebellum development. TMSB10 is only present at very low levels in a very small subpopulation of glia in the adult cerebellum. In young animals, most of the TMSB10 is localized in granule cells, Golgi neurons and Purkinje cells. In old animals, TMSB10 signal is detected faintly in a few Purkinje cells(Hall AK et al.,1990; Lin SC et al.,1990; Hall AK,1991; Hall AK et al.,1991; Lin SC et al.,1991; Lugo DI et al., Condon MR et al.,1992; Border BG et al., 1993; Voisin PJ et al., 1995; Carpintero P et al.,1996 ;Carpintero P et al.,1999; Anadon R et al.,2001; Bani-Yaghoub M et al.,2001; Gomez-Marquez J et al.,2002;T okuriki M et al.,2003; Nemolato S et al.,2009; Gerosa C et al.,2010; Fanni D et al.,2011; Shiotsuka M et al.,2013).

Apoptosis: TMSB10 regulates apoptosis. For example, upregulation of TMSB10 in M. bovis-infected macrophages is linked with increased cell death due to apoptosis. TMSB10 can disrupt F-actin stress fibers, markedly decrease ovarian cancer cells growth, and a high rate of apoptosis. TMSB10 plays a significant role in cell apoptosis possibly by acting as an actin-mediated tumor suppressor, perhaps functions as a neoapoptotic influence during embryogenesis, and may mediate some of the pro-apoptotic anticancer actions of retinoids(Hall AK,1995; Gutierrez-Pabello JA et al.,2002; Rho SB et al.,2004; Lee SH et al.,2005; Rho SB et al.,2005)..

Angiogenesis: TMSB10 may be an effective inhibitor of angiogenesis by inhibiting endothelial migration, tube formation, VEGF, VEGFR-1 and integrin alphaV expression in HCAECs. TMSB10 is not only a cytoskeletal regulator, it also acts as a potent inhibitor of angiogenesis and tumor growth by interaction with Ras (Koutrafouri V et al.,2001; Vasile E et al.,2001; Zhang Y et al.,2009).

Cancers: Elevated expression of TMSB10 is associated with invasion and metastasis of several kinds of tumors. It may be considered a potential tool for the diagnosis of several human neoplasias. TMSB10 is detected mainly in the malignant tissue, particularly in the cancerous cells, whereas the normal cell population around the lesions showed very weak staining. Also, the intensity of staining in the cancerous cells is proportionally increased with the increasing grade of the lesions(Santelli G et al.,1999; Sribenja S et al., 2009; Sribenja S et al.,2013).

Homology

Implicated in

Entity
Pancreatic cancer
Note
TSMB10 is expressed in human pancreatic carcinoma, but not in non-neoplastic pancreatic tissue, suggesting a role for TMSB10 in the carcinogenesis of pancreatic carcinoma. It is a promising marker and a novel therapeutic target for pancreatic cancer. Exogenous TMSB10 causes the phosphorylation of JNK and increases the secretion of cytokines interleukin (IL)-7 and IL-8 in BxPC-3 pancreatic cancer cells (Alldinger I et al., 2005; Li M et al.,2009).
Entity
Non-small cell lung cancer
Note
TMSB10 might induce microvascular and lymphatic vessel formation by up-regulating vascular endothelial growth factor and vascular endothelial growth factor-C in lung cancer tissues, thus promoting the distant and lymph node metastases and being implicated in the progression of non-small cell lung cancer. TMSB10 hypomethylation may be frequently in NSCLCs, but it may not be a common mechanism of TMSB10 overexpression (Gu Y et al., 2009; Lee SM et al., 2011).
Entity
Breast cancer
Note
TMSB10 plays a key role in sequestration of G-actin as well as in breast cancer cell motility (Verghese-Nikolakaki S et al., 1996; Otto AM et al., 2002; Maelan AE et al., 2007).
Entity
Ovarian cancer
Note
TMSB10 inhibits angiogenesis and tumor growth by interfering Ras signal transduction and expression of VEGF. TMSB10 decreased mitochondrial membrane potential and increased reactive oxygen species (ROS) production of human ovarian cancer cells. Also these findings indicate that upregulation of ROS production due to TMSB10 overexpression increases ovarian cancer cells apoptosis (Lee SH et al., 2001; Kim YC et al., 2012).
Entity
Thyroid neoplasias
Note
TMSB10 overexpression is a general event of thyroid cell neoplastic transformation. An increased expression of TMSB10 mRNA in thyroid carcinomas is found. The evaluation of TMSB10 gene expression may be considered a promising means of human thyroid hyperproliferative diagnosis. By decreasing TMSB10 expression, the thyroid cancer cells growth in soft agar is inhibited. . In papillary thyroid neoplasias, high expressions of TMSB10 mRNA and protein are more common in patients with cervical lymph node metastases (LNM) and central neck LNM (Califano D et al., 1998; Viglietto G et al., 1999; Santelli G et al., 2002; Takano T et al., 2002; Chiappetta G et al., 2004; Feher LZ et al., 2012; Zhang XJ et al., 2014).
Entity
Renal cell carcinoma
Note
The TMSB10 gene is deregulated in renal cell carcinoma and it may be a new molecular marker for renal-cell carcinoma (Ren Fail, 1994).
Entity
Cutaneous melanoma
Note
TMSB10 can be considered as a new progression marker for human cutaneous melanoma (Weterman MA et al., 1993).
Entity
Hepato cellular carcinoma
Note
The expression levels of TMSB10 mRNA and protein are significantly higher in hepatocellular carcinoma tissues than those in matched non-tumorous tissues. High expression of TMSB10 is significantly associated with advanced TNM stage and poorer survival in hepatocellular carcinoma patients (Wang H et al., 2014).
Entity
Cholangiocarcinoma
Note
Low expression of TMSB10 is associated with metastasis of cholangiocarcinoma in vitro and in vivo. TMSB10 expression may be mediated by the activation of Ras, ERK1/2. TMSB10 can upregulates Snail andmatrix metalloproteinases (MMPs) expressions (Sribenja S et al., 2013).
Entity
Cervical cancer
Note
TMSB10 gene can predict pelvic lymph node metastasis (PLNM) in patients with early cervical carcinoma (Huang L et al., 2011).

Bibliography

Pubmed IDLast YearTitleAuthors
34938511986Synthesis of deacetyl-thymosin beta 10 and examination of its immunological effect on T-cell subpopulations of a uremic patient with tuberculosis.Abiko T et al
159834442005Gene expression analysis of pancreatic cell lines reveals genes overexpressed in pancreatic cancer.Alldinger I et al
112511992001Differential expression of thymosins beta(4) and beta(10) during rat cerebellum postnatal development.Anadón R et al
115272082001Array analysis of the genes regulated during neuronal differentiation of human embryonal cells.Bani-Yaghoub M et al
82459651993Alterations in actin-binding beta-thymosin expression accompany neuronal differentiation and migration in rat cerebellum.Border BG et al
94850411998Thymosin beta-10 gene overexpression correlated with the highly malignant neoplastic phenotype of transformed thyroid cells in vivo and in vitro.Califano D et al
103815521999Expression of the thymosin beta10 gene in normal and kainic acid-treated rat forebrain.Carpintero P et al
152546832004Thymosin beta-10 gene expression as a possible tool in diagnosis of thyroid neoplasias.Chiappetta G et al
16274601992Expression of thymosin beta-4 and related genes in developing human brain.Condon MR et al
65787031983Thymosin beta 10, a new analog of thymosin beta 4 in mammalian tissues.Erickson-Viitanen S et al
128823582002The beta-thymosins, small actin-binding peptides widely expressed in the developing and adult cerebellum.Gómez-Márquez J et al
36061311987Molecular cloning of the cDNA for rat spleen thymosin beta 10 and the deduced amino acid sequence.Goodall GJ et al
187894852009Expression of thymosin beta10 and its role in non-small cell lung cancer.Gu Y et al
118959782002Upregulation of thymosin beta-10 by Mycobacterium bovis infection of bovine macrophages is associated with apoptosis.Gutiérrez-Pabello JA et al
18463971991Retinoic acid regulates thymosin beta 10 levels in rat neuroblastoma cells.Hall AK et al
21695661990Thymosin beta 10 levels in developing human brain and its regulation by retinoic acid in the HTB-10 neuroblastoma.Hall AK et al
85897571995Thymosin beta-10 accelerates apoptosis.Hall AK et al
93057281997C-terminal truncation of thymosin beta10 by an intracellular protease and its influence on the interaction with G-actin studied by ultrafiltration.Huff T et al
117310862001Effect of thymosin peptides on the chick chorioallantoic membrane angiogenesis model.Koutrafouri V et al
156652892005Thymosin {beta}(10) inhibits angiogenesis and tumor growth by interfering with Ras function.Lee SH et al
117097042001Overexpression of the thymosin beta-10 gene in human ovarian cancer cells disrupts F-actin stress fiber and leads to apoptosis.Lee SH et al
191948242009Thymosin beta-10 is aberrantly expressed in pancreatic cancer and induces JNK activation.Li M et al
17441291991Cloning and characterization of a testis-specific thymosin beta 10 cDNA. Expression in post-meiotic male germ cells.Lin SC et al
149752052004Differential thymosin beta 10 expression levels and actin filament organization in tumor cell lines with different metastatic potential.Liu CR et al
19885501991Developmental regulation of beta-thymosins in the rat central nervous system.Lugo DI et al
167863222007Localization of thymosin beta10 in breast cancer cells: relationship to actin cytoskeletal remodeling and cell motility.Maelan AE et al
33652561988Sequence of a human kidney cDNA clone encoding thymosin beta 10.McCreary V et al
164963022006Thymosin beta10 inhibits cell migration and capillary-like tube formation of human coronary artery endothelial cells.Mu H et al
84480311993Small actin-binding proteins: the beta-thymosin family.Nachmias VT et al
193373642009Thymosin beta(4) and beta(10) levels in pre-term newborn oral cavity and foetal salivary glands evidence a switch of secretion during foetal development.Nemolato S et al
120294402002Chemotherapeutic drugs change actin skeleton organization and the expression of beta-thymosins in human breast cancer cells.Otto AM et al
147413412004The interaction between E-tropomodulin and thymosin beta-10 rescues tumor cells from thymosin beta-10 mediated apoptosis by restoring actin architecture.Rho SB et al
160121742005The identification of apoptosis-related residues in human thymosin beta-10 by mutational analysis and computational modeling.Rho SB et al
124819412002Thymosin beta-10 protein synthesis suppression reduces the growth of human thyroid carcinoma cells in semisolid medium.Santelli G et al
123245712002Quantitative analysis of thymosin beta-10 messenger RNA in thyroid carcinomas.Takano T et al
127923152003Gene expression analysis of human middle ear cholesteatoma using complementary DNA arrays.Tokuriki M et al
111569612001Differential expression of thymosin beta-10 by early passage and senescent vascular endothelium is modulated by VPF/VEGF: evidence for senescent endothelial cells in vivo at sites of atherosclerosis.Vasile E et al
104471021999Investigation of the epitopic structure of thymosin beta10 by epitope mapping experiments.Vassiliadou I et al
89125421996Preliminary findings on the expression of thymosin beta-10 in human breast cancer.Verghese-Nikolakaki S et al
103664161999Regulation of thymosin beta10 expression by TSH and other mitogenic signals in the thyroid gland and in cultured thyrocytes.Viglietto G et al
77989041995Developmental characterization of thymosin beta 4 and beta 10 expression in enriched neuronal cultures from rat cerebella.Voisin PJ et al
84257651993Thymosin beta-10 expression in melanoma cell lines and melanocytic lesions: a new progression marker for human cutaneous melanoma.Weterman MA et al
81941071994Effects of thymosin beta 4 and thymosin beta 10 on actin structures in living cells.Yu FX et al
188546592009Overexpression of thymosin beta-10 inhibits VEGF mRNA expression, autocrine VEGF protein production, and tube formation in hypoxia-induced monkey choroid-retinal endothelial cells.Zhang T et al

Other Information

Locus ID:

NCBI: 9168
MIM: 188399
HGNC: 11879
Ensembl: ENSG00000034510

Variants:

dbSNP: 9168
ClinVar: 9168
TCGA: ENSG00000034510
COSMIC: TMSB10

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000034510ENST00000233143P63313

Expression (GTEx)

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References

Pubmed IDYearTitleCitations
281790172017Thymosin beta 10 is a key regulator of tumorigenesis and metastasis and a novel serum marker in breast cancer.35
156652892005Thymosin {beta}(10) inhibits angiogenesis and tumor growth by interfering with Ras function.15
187894852009Expression of thymosin beta10 and its role in non-small cell lung cancer.13
193373642009Thymosin beta(4) and beta(10) levels in pre-term newborn oral cavity and foetal salivary glands evidence a switch of secretion during foetal development.11
247049912014Thymosin beta 4 and thymosin beta 10 expression in hepatocellular carcinoma.11
226239512012Thymosin β10 expression driven by the human TERT promoter induces ovarian cancer-specific apoptosis through ROS production.10
167863222007Localization of thymosin beta10 in breast cancer cells: relationship to actin cytoskeletal remodeling and cell motility.9
221610242012Amplification of thymosin beta 10 and AKAP13 genes in metastatic and aggressive papillary thyroid carcinomas.9
240533802013Suppression of thymosin β10 increases cell migration and metastasis of cholangiocarcinoma.9
191948242009Thymosin beta-10 is aberrantly expressed in pancreatic cancer and induces JNK activation.8

Citation

Xueshan Qiu ; Yumei Gu

TMSB10 (thymosin beta 10)

Atlas Genet Cytogenet Oncol Haematol. 2014-12-01

Online version: http://atlasgeneticsoncology.org/gene/42595/tmsb10

Historical Card

2010-03-01 TMSB10 (thymosin beta 10) by  Xueshan Qiu 

Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China