Effect of integrin alpha 7 on cell proliferation, invasion, apoptosis and the PI3K/AKT pathway, and its association with clinicopathological features in endometrial cancer

Targeting integrin alpha 7 (ITGA7) suppresses malignant progression of several types of cancer, including tongue squamous cell carcinoma, hepatocellular carcinoma and non-small cell lung cancer, while the effect of its knockdown on cell function and its association with clinicopathological features in endometrial cancer (EC) is unclear. The present study aimed to investigate this issue. ITGA7 was knocked down by short-interfering (si)RNA in Ishikawa and RL95-2 cells followed by western blotting and reverse transcription-quantitative PCR assays. Subsequently, cell proliferation, apoptosis, invasion and expression levels of PI3K, phosphorylated (p-) PI3K, AKT and p-AKT were determined using Cell Counting Kit-8, TUNEL, Transwell assays and western blotting. Moreover, ITGA7 in tumor and adjacent tissues from 50 patients with endometrial cancer was detected using immunohistochemical assay. ITGA7 expression was increased in EC cell lines (HEC-1A, RL95-2, Ishikawa and KLE) compared with telomerase-immortalized human endometrial stromal cells (THESCs). In both Ishikawa and RL95-2 cells, three ITGA7 siRNAs all demonstrated good efficiency on ITGA7 knockdown, amongst which the one with the highest efficiency was selected for the following experiments. ITGA7 knockdown reduced cell proliferation and invasion, while inducing apoptosis; moreover, it suppressed p-PI3K/PI3K and p-AKT/AKT ratios. In patients with EC, ITGA7 expression was increased in tumor tissues compared with adjacent tissues, and its lower tumor expression was associated with myometrial invasion (< 1/2), non-lymphovascular invasion and decreased FIGO stage. In conclusion, ITGA7 knockdown repressed proliferation, invasion and the PI3K/AKT pathway while inducing apoptosis in EC cell lines, and its insufficiency was associated with less advanced tumor features in EC patients. These results indicated that ITGA7 may be a potential target for the treatment of EC.