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

Abstract

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.

Downregulation of LIMK1–ADF/cofilin by DADS inhibits the migration and invasion of colon cancer

“…It reduces the activation of depolymerization of ADF/cofilin. This subsequently interferes with actin depolymerization, promotes actin cytoskeletal remodeling and cell pseudopodia formation, and induces EMT, thereby promoting tumor invasion and metastasis3649. The present study further confirmed that the expression and phosphorylation levels of LIMK1 significantly increased during colon cancer cell invasion and migration.…”

Thymosin β4 Regulates Focal Adhesion Formation in Human Melanoma Cells and Affects Their Migration and Invasion

“…It was shown for hepatoblastoma and oral squamous cell carcinoma that Tβ4 induced EMT transition (Fu et al, 2015;Hong et al, 2016). Here, we demonstrate that also in melanoma cells there is a connection between TMSB4X expression and EMT progression.…”

The Progress of Diallyl Disulfide in Anti-Cancer

“…DADS downregulates LIM kinase-1 (LIMK1), vimentin and EMTrelated proteins (Slug, Snail), and upregulates E-cadherin and TIMP-3 (tissue inhibitor of metalloproteinase-3) expression which are the signs of the occurrence of EMT, suggesting that DADS may reverse EMT by downregulating LIMK1 [97,98]. DADS suppresses actin cytoskeletal remodeling and cell pseudopodia formation, and the occurrence of EMT via down regulating LIMK1 expression to decrease the expression of vimentin, CD34, and Ki-67; increase E-cadherin expression; and impede cancer cell proliferation, angiogenesis, and EMT alteration, thereby inhibiting invasion and metastasis [98][99][100]. Actually, the effects of DADS on E-cadherin and vimentin expression may result in blockage of the ERK/Fra-1 pathway by inhibition of LIMK1 expression and activity.…”