CD82/KAI1 inhibits invasion and metastasis of esophageal squamous cell carcinoma via TGF-β1.

OBJECTIVE: Previous studies have found that CD82/KAI1 is a tumor suppressor gene. However, the role of CD82/KAI1 in esophageal squamous cell carcinoma (ESCC) has not been reported. This study aims to investigate the specific role of CD82/KAI1 in ESCC, so as to further explore the relationship between CD82/KAI1 expression and clinical characteristics of ESCC.

PATIENTS AND METHODS: The expression of CD82/KAI1 in 96 pairs of ESCC tissues and adjacent normal tissues was detected by Real-time quantitative polymerase chain reaction (qRT-PCR). The relationship between CD82/KAI1 expression and the pathological indicators of ESCC patients was analyzed by Kaplan-Meier method. QRT-PCR further validated the expression level of CD82/KAI1 in ESCC cells. In addition, the CD82/KAI1 knockdown expression model was constructed using small interfering RNA in ESCC cell lines TE-1 and EC-109 cells. Cell counting kit-8 (CCK-8) and transwell assay were performed to detect cell viability, invasion and migration. Finally, the potential mechanism of CD82/KAI1 in regulating ESCC was explored using Western blot.

RESULTS: QRT-PCR results showed that the expression level of CD82/KAI1 in ESCC was significantly lower than that of normal tissues, and the difference was statistically significant. Higher rates of lymph node metastasis and distant metastasis, as well as shorter overall survival were observed in ESCC patients with lower expression of CD82/KAI1 compared with those with higher expression. CD82/KAI1 overexpression decreased cell proliferation, invasion and metastasis in ESCC cells. Western blot results showed that the expressions of TGF-β1, Smad2/3, MMP-2 and MMP-9 were regulated by CD82/KAI1. In addition, rescue experiments demonstrated an interaction between CD82/KAI1 and TGF-β1, indicating that CD82/KAI1 inhibits the malignant progression of ESCC via regulating TGF-β1.

CONCLUSIONS: Lowly expressed CD82/KAI1 in ESCC was significantly associated with the pathological stage, distant metastasis and poor prognosis of ESCC patients. CD82/KAI1 may inhibit the malignant progression of ESCC by interacting with TGF-β1.