Transgelin 2 promotes paclitaxel resistance, migration and invasion of breast cancer by directly interacting with PTEN and activating PI3K/Akt/GSK-3β pathway.

MDR and tumor migration and invasion are still the main obstacles to effective breast cancer chemotherapies. Transgelin 2 has recently been shown to induce drug resistance, tumor migration, and invasion. The aim of this study was to determine the biological functions of Transgelin 2 and the mechanism underlying how Transgelin 2 induces paclitaxel (PTX) resistance and the migration and invasion of breast cancer. We detected that the protein level of Transgelin 2 was significantly upregulated in breast cancer tissues compared with adjacent nontwnor tissues. A bioinformatics analysis indicated that Transgelin 2 was significantly related to dinicopathologic parameters and patient prognosis. Overexpression of Transgelin 2 enhanced the migration and invasion of human breast cancer cells and decreased the sensitivity of breast cancer cells to paditaxel. Meanwhile, the tumorigenesis and metastasis of breast cancer cells were also enhanced by Transgelin 2 overexpression in vivo. Moreover, Transgelin 2 overexpression activated the PI3K/Akt/GSK-3 beta pathway by increasing the phosphorylation levels of Akt and GSK-30 and decreasing the expression of PTEN. We also found that Transgelin 2 could directly interact with PTEN and was located upstream of PTEN. Furthermore, the PI3K/Akt pathway inhibitor MK-2206 reversed the resistance to paclitaxel and inhibited the migration and invasion of breast cancer cells. These findings indicate that Transgelin 2 promotes paditaxel resistance and the migration and invasion of breast cancer by directly interacting with PTEN and activating the PI3K/Akt/GSK-3 beta pathway. Transgelin 2 may therefore be useful as a novel biomarker and therapeutic target for breast cancer.