Roles and Mechanisms of β-Thymosins in Cell Migration and Cancer Metastasis: An Update

Sribenja, Sirinapa; Wongkham, Sopit; Wongkham, Chaisiri; Yao, Qizhi; Chen, Changyi

doi:10.3109/07357907.2012.756111

Cited by 50 publications

(44 citation statements)

References 123 publications

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“…Tbeta10, as a member of the β-thymosin family, is the main intracellular G actin-sequestering protein involved in cell proliferation, migration, and differentiation [6-8]. Many reports described the potential functional roles of Tbeta10 in human cancers.…”

Section: Discussionmentioning

confidence: 99%

“…Tbeta10 is a member of the β-thymosin family, which is widely distributed in many tissues, with proven biological activities as an actin-sequestering protein involved in cell motility. In recent years, Tbeta10 has been proposed as a multifunctional regenerative peptide [5] that is involved in many critical biological activities including cell proliferation, anti-apoptosis and angiogenesis [6-8]. In cancer study, the role of Tbeta10 is controversial.…”

Section: Introductionmentioning

confidence: 99%

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High expression of thymosin beta 10 predicts poor prognosis for hepatocellular carcinoma after hepatectomy

et al. 2014

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BackgroundThymosin beta 10 (Tbeta10) overexpression has been reported in a variety of human cancers. However, the role of Tbeta10 in hepatocellular carcinoma (HCC) remains unclear. The aim of the present study was to analyze Tbeta10 expression in tumor and matched non-tumorous tissues, and to assess its prognostic significance for HCC after hepatectomy.MethodsThe level of Tbeta10 mRNA and protein in tumor and matched non-tumorous tissues was evaluated in 26 fresh HCC cases by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Additionally, Tbeta10 protein expression in 196 HCC was analyzed by immunohistochemistry (IHC) and correlated with clinicopathological characteristics and survival.ResultsResults from RT-PCR and western blot analysis show that the levels of Tbeta10 mRNA and protein were significantly higher in tumor tissues of HCC, compared to that in matched non-tumorous tissues (P = 0.01 and P <0.001, respectively). IHC staining showed that high expression of Tbeta10 was detected in 58.2% (114/196) of HCC cases. High expression of Tbeta10 was significantly associated with advanced TNM stage (P <0.001). Survival analysis demonstrated that high Tbeta10 was related to shorter overall survival (OS) (P = 0.000) and disease-free survival (DFS) (P = 0.000). Multivariate analysis showed that high expression of Tbeta10 was an independent prognostic factor for both OS (P = 0.001, HR = 4.135, 95% CI: 2.603 to 6.569) and DFS (P = 0.001, HR = 2.021, 95% CI: 1.442 to 2.832). Subgroup analysis revealed that high expression of Tbeta10 predicts poorer survival for early and advanced stage.ConclusionsTbeta10 protein abnormal expression might contribute to the malignant progression of HCC. High expression of Tbeta10 predicts poor prognosis in patients with HCC after hepatectomy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High expression of thymosin beta 10 predicts poor prognosis for hepatocellular carcinoma after hepatectomy

et al. 2014

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“…Actin and its associated proteins are units for cell migration and cytoskeleton remodeling, and their assembly process is modulated by a large number of actin-binding proteins (ABPs) (Sribenja et al 2013). One of the representative proteins of ABPs is thymosin β4 (Tβ4), a highly conserved acidic 5 kDa N-terminally acetylated peptide.…”

Section: Introductionmentioning

confidence: 99%

Thymosin β4 induces proliferation, invasion, and epithelial-to-mesenchymal transition of oral squamous cell carcinoma

et al. 2015

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The epithelial-to-mesenchymal transition (EMT) plays a vital role in carcinogenesis, invasion, and metastasis of many epithelial tumors including oral squamous cell carcinoma (OSCC), a common malignancy of the head and neck. However, the functional role of the actin-sequestering protein thymosin β4 (Tβ4) in the EMT in OSCCs remains unclear. Thus, we investigated whether overexpression of Tβ4 could induce in vitro tumorigenesis such as cell proliferation and anchorage independency and an EMT-like phenotype in OSCCs. Also, we examined whether it affects invasiveness and cell motility-associated signaling molecules. Tβ4-overexpressing OSCCs, SCC-15_Tβ4 and SCC-25_Tβ4, enhanced cell proliferation and colony formation. In addition, we observed that Tβ4 overexpression induced an EMT-like phenotype, accompanied by a decrease in expression of the epithelial cell marker E-cadherin and an increase in expression of mesenchymal cell markers vimentin and N-cadherin. Also, the expression level of Twist1, an EMT-inducing transcription factor, was significantly enhanced in SCC-15_Tβ4 and SCC-25_Tβ4 cells. Tβ4 overexpression augmented in vitro invasion and MMP-2 activity and enhanced the phosphorylation of paxillin and cortactin and expression of LIMK1. Taken together, these results suggest that Tβ4 overexpression could be one of the causes of tumorigenesis and progression in OSCCs. Further investigation on the Tβ4 molecule would encourage the development of specific targets for cancer treatment.

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“…It has been reported that TB4 can activate the survival kinase Akt and play a potent role in the protection of cardiac muscle from cell death after ischemic damage, as occurs in the setting of myocardial infarction (MI) (Bock-Marquette et al, 2004). TB4 can also promote angiogenesis in ischemic areas (Bock-Marquette et al, 2009; Smart et al, 2006), contribute to heart wound healing (Malinda et al, 1997; 1999) and promote cancer metastasis (Sribenja et al, 2013) and inflammatory responses (Huff et al, 2001; Sosne et al, 2002). Furthermore, TB4 has been reported to prime epicardium-derived progenitors to differentiate into cardiomyocytes (Smart et al, 2011) or coronary vessels (Bock-Marquette et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Thymosin Beta4 Regulates Cardiac Valve Formation Via Endothelial-Mesenchymal Transformation in Zebrafish Embryos

Shin

Lee

Bae

et al. 2014

Molecules and Cells

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Thymosin beta4 (TB4) has multiple functions in cellular response in processes as diverse as embryonic organ development and the pathogeneses of disease, especially those associated with cardiac coronary vessels. However, the specific roles played by TB4 during heart valve development in vertebrates are largely unknown. Here, we identified a novel function of TB4 in endothelialmesenchymal transformation (EMT) in cardiac valve endocardial cushions in zebrafish. The expressions of thymosin family members in developing zebrafish embryos were determined by whole mount in situ hybridization. Of the thymosin family members only zTB4 was expressed in the developing heart region. Cardiac valve development at 48 h post fertilization was defected in zebrafish TB4 (zTB4) morpholino-injected embryos (morphants). In zTB4 morphants, abnormal linear heart tube development was observed. The expressions of bone morphogenetic protein (BMP) 4, notch1b, and hyaluronic acid synthase (HAS) 2 genes were also markedly reduced in atrio-ventricular canal (AVC). Endocardial cells in the AVC region were stained with anti-Zn5 antibody reactive against Dm-grasp (an EMT marker) to observe EMT in developing cardiac valves in zTB4 morphants. EMT marker expression in valve endothelial cells was confirmed after transfection with TB4 siRNA in the presence of transforming growth factor β (TGFβ) by RT-PCR and immunofluorescent assay. Zn5-positive endocardial AVC cells were not observed in zTB4 morphants, and knockdown of TB4 suppressed TGF-β-induced EMT in ovine valve endothelial cells. Taken together, our results demonstrate that TB4 plays a pivotal role in cardiac valve formation by increasing EMT.

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Roles and Mechanisms of β-Thymosins in Cell Migration and Cancer Metastasis: An Update

Cited by 50 publications

References 123 publications

High expression of thymosin beta 10 predicts poor prognosis for hepatocellular carcinoma after hepatectomy

High expression of thymosin beta 10 predicts poor prognosis for hepatocellular carcinoma after hepatectomy

Thymosin β4 induces proliferation, invasion, and epithelial-to-mesenchymal transition of oral squamous cell carcinoma

Thymosin Beta4 Regulates Cardiac Valve Formation Via Endothelial-Mesenchymal Transformation in Zebrafish Embryos

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