Tropomodulin 3 promotes liver cancer progression by activating the MAPK/ERK signaling pathway

Abstract

Tropomodulin 3 (TMOD3) is a member of the pointed-end capping protein family that contributes to invasion and metastasis in several types of malignancies. TMOD3 has been found to be crucial for membranous skeleton and embryonic development; however, little is known regarding the role of TMOD3 in liver cancer progression. In addition, to the best of our knowledge, no previous studies have investigated the mechanism underlying the TMOD3-regulated promotion of liver cancer. The aim of the present study was to determine whether TMOD3 is associated with liver cancer progression. TMOD3 expression was found to be elevated in liver cancer cells and tissues. In the in vitro experiments, liver cancer cell proliferation, invasion and migration were inhibited by TMOD3 knockdown and promoted by ectopic expression of TMOD3. Furthermore, mechanistic analysis indicated that TMOD3 overexpression activated mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling and increased the levels of other targets of this pathway, including matrix metalloproteinase (MMP)2, MMP9 and cyclin D1. TMOD3 overexpression was associated with changes in liver cancer cell morphology and altered expression of epithelial and mesenchymal markers. High TMOD3 expression was hypothesized to promote epithelial-to-mesenchymal transition in liver cancer cells. In conclusion, TMOD3 was shown to promote liver cancer cell growth, invasion and migration through the MAPK/ERK signaling pathway, and it may serve as a candidate biomarker and therapeutic target in liver cancer.