Inhibition of integrin subunit alpha 11 restrains gastric cancer progression through phosphatidylinositol 3-kinase/Akt pathway

Gastric cancer (GC) is among the most frequent malignancies originating from the digestive system worldwide, while the role and specific mechanism of integrin-subunit alpha 11 (ITGA11) in GC remain unclear. This study probes the expression characteristics and function of ITGA11 in GC. Firstly, the ITGA11 profile in GC tissues and paracancerous non-tumor tissues was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot (WB), and the association between ITGA11 and GC patients' clinicopathological indicators was evaluated. ITGA11 knockdown models were set up in GC cell lines MKN45 and AGS. Cell proliferation was determined by the cell counting kit-8 (CCK-8) assay and colony formation assay. WB was utilized to gauge the expression of apoptosis-related proteins (Bax, Bcl2, Bad, and C-Caspase3) and the PI3K/AKT pathway. We discovered that the ITGA11 expression was boosted in GC tissues and was related to the unfavorable prognosis of GC patients. Additionally, ITGA11 knockdown abated GC cell proliferation, invasion and migration, and enhanced cell apoptosis. In animal experiments, the tumorigenesis of GC cells knocking down ITGA11 was reduced. Mechanically, knocking down ITGA11 notably inactivated the PI3K/AKT axis. The tumor-suppressive effect mediated by ITGA11 knockdown was attenuated after activating the PI3K/AKT pathway with insulin-like growth factor 1 (IGF-1). Overall, this study substantiated that the ITGA11 expression was heightened in GC tissues, which affected GC progression by modulating the PI3K/AKT pathway.

Automated summary

This study revealed that the expression of ITGA11 was elevated in gastric cancer tissues and associated with poor prognosis. Knocking down ITGA11 inhibited cell proliferation, invasion, and migration while promoting apoptosis in gastric cancer cells. The tumor-suppressive effect of ITGA11 knockdown may be mediated by inactivation of the PI3K/AKT pathway.