ING5 Inhibits Migration and Invasion of Esophageal Cancer Cells by Downregulating the IL-6/CXCL12 Signaling Pathway.

Abstract

Esophageal squamous cell carcinoma (ESCC) is a common cancer in East Asia and in other parts of the world and exhibits a poor prognosis. Growth inhibitor 5 (ING5) is a new member of the growth inhibitor (ING) protein family and is involved in many important cellular functions, such as the cell cycle, apoptosis, and chromatin remodeling. As a newly discovered tumor suppressor, ING5 has been shown to inhibit lung cancer proliferation and distant metastasis through the AKT pathway. In lung cancer tumors, ING5 can attenuate the ability of cancer cells to invade normal tumor-adjacent tissues. However, ING5 has rarely been studied in ESCC. Here, we found that in ESCC EC-109 cancer cells, ING5 overexpression inhibited cell proliferation and tumor invasion, whereas, in ESCC TE-1 cancer cells, ING5 knockdown promoted cell invasion. In a nude mouse xenograft model, ING5 overexpression inhibited tumor growth and the invasion ability of ESCC cells. Further studies revealed that ING5 overexpression inhibited IL-6/CXCL12 expression at both the mRNA and protein levels as well as morphological changes. We found for the first time that ING5 inhibits ESCC cell migration and invasion by downregulating the IL-6/CXCL12 signaling pathway.