Integrin-linked kinase affects the sensitivity of esophageal squamous cell carcinoma cells to chemotherapy with cisplatin via the Wnt/beta-catenin signaling pathway.

Recent studies have shown that the expression of integrin-linked kinase (ILK) was related to the occurrence, development, and malignant progression of esophageal squamous cell carcinoma (ESCC). However, research on the relationship between ILK and the chemosensitivity of ESCC has to date not been reported. The present study found that ILK was highly expressed in ESCC cell lines, and the overexpression of ILK in ESCC cells reduced the incidence of cell apoptosis and alleviated the cytotoxicity on cells induced by cisplatin (CDDP). Inversely, ILK knockdown increased CDDP-induced apoptosis and had an inhibitive effect on the malignant phenotype of ESCC, including cell proliferation, invasion, and migration. In addition, ILK knockdown in ESCC cells inhibited the expression of beta (ß)-catenin and activated the wingless/integrated (Wnt) signaling pathway. Furthermore, cellular MYC (c-MYC) and Cylin D1 were the target genes of the Wnt signaling pathway. Rescue experiments showed that the overexpression of ß-catenin reversed a tumor's inhibition and apoptosis abilities induced by ILK knockdown. In conclusion, ILK potentially reduced the CDDP sensitivity of ESCC cells by influencing the activity of the Wnt/ß-catenin signaling pathway.

ILK predicts the efficacy of chemoradiotherapy and the prognosis of patients with esophageal squamous cell carcinoma.

Isobaric tags for relative and absolute quantitation (iTRAQ) technology was adopted to screen differentially-expressed proteins in the serum that predict the effects of chemoradiotherapy on esophageal squamous cell carcinoma (ESCC). Thus, significantly related proteins can be functionally identified at the cellular level. A total of 60 patients diagnosed with locally advanced and advanced ESCC were recruited and treated with chemoradiotherapy. The iTRAQ technique was used to screen serum differentially expressed proteins associated with chemoradiotherapeutic efficacy. Functional identification of significantly related proteins was performed at the cellular level. Cell proliferation was detected using MTT, clonogenic and fluorescence assays, and apoptosis was assessed using flow cytometry. Transwell and wound-healing assays were used to detect the invasion and migration properties of cancer cells. Proteomics results revealed that prior to chemoradiotherapy, the expression level of integrin-linked kinase (ILK) was significantly upregulated in patients with ESCC, compared with that of the control group [ratio (r)=4.386; P<0.05], and significantly downregulated in the chemoradiotherapy-sensitive group, compared with the chemoradiotherapy-resistant group (r=0.587; P<0.05). At the cellular level, the proliferation rate of cells in the experimental group was significantly inhibited (P<0.05), and the number of cell colonies was decreased (P<0.01), while the number of apoptotic cells was significantly increased (P<0.01). The invasive ability of TE-1 cells in the shILK group was significantly inhibited (P<0.01), and the migration rate was significantly retarded at 8 and 24 h (P<0.01). The present study highlighted the potential value of ILK in predicting the efficacy of chemoradiotherapeutic treatment in patients with ESCC, and that ILK gene-silencing inhibits the progression of ESCC.