Upregulation of SIX4 indicates poor clinical outcome and promotes tumor growth and cell metastasis in esophageal squamous cell carcinoma

Background The role of sine oculis homeobox 4 (SIX4) has been found in some malignant tumors. However, there have been few studies on the function of SIX4 in esophageal squamous cell carcinoma (ESCC). This study aimed to explore the regulatory mechanism of SIX4 in ESCC. Methods RT‐qPCR and Western blot analysis were used to measure mRNA and protein expression. The function of SIX4 was investigated using CCK‐8, colony formation, flow cytometry, wound healing and transwell assays. A mouse xenograft tumor assay was designed to perform in vivo experiments. Results SIX4 was upregulated in ESCC and indicated poor clinical outcomes in ESCC patients. Functionally, knockdown of SIX4 inhibited cell proliferation and induced apoptosis in ESCC. In addition, the silencing of SIX4 inhibited cell migration, invasion and EMT in ESCC. More importantly, upregulation of SIX4 could activate the PI3K/AKT pathway in ESCC cells and promote tumor growth in vivo. Conclusions Upregulation of SIX4 indicates poor clinical outcomes in ESCC patients and promotes tumor growth and cell metastasis in ESCC. 1. SIX4 was upregulated in ESCC and indicated poor clinical outcomes in ESCC patients. 2. SIX4 promotes tumor growth and cell metastasis in ESCC. 3. Upregulation of SIX4 could activate the PI3K/AKT pathway in ESCC cells.