Konishi T, Shiozaki A, Kosuga T, et al. - Whether leucine-rich repeat–containing protein A (LRRC8A) has a role in the growth of esophageal squamous cell carcinoma (ESCC), as well as has prognostic value in this tumor, was investigated by undertaking knockdown experiments using ESCC cell lines and LRRC8A siRNA. From ESCC patients receiving radical esophagectomy, 64 primary tumor samples were analyzed using immunohistochemistry. Reduction in cell proliferation and migration and promotion of apoptosis were induced by LRRC8A depletion. By microarray data, G₁/S checkpoint regulation and up-regulation or down-regulation of phosphatidylinositol 3-kinase/AKT signaling, matrix metalloproteinase, and integrin signaling–related genes (including p21, p27, MMP1, and ITGAV) was evident in LRRC8A-depleted cells. On immunohistochemistry, a link was found between LRRC8A expression and pathologic N and T stage categories, and a correlation was observed between strong LRRC8A expression and a worse prognosis. By impacting cell cycle, apoptosis, and migration, LRRC8A behaved as a modulator of tumor progression in ESCC. These findings offer novel information on the function of LRRC8A as an effector or biomarker of ESCC.