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

Abstract

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.

Clinical Presentation and Prognostic Features in Patients with Immunotherapy-Induced Vitiligo-like Depigmentation: A Monocentric Prospective Observational Study

“…Integrin α11 (ITGA11) is a known receptor for collagen. The role of this protein has been shown, especially in lung cancer and gastric cancer tissue, as being associated with tumor progression [ 25 , 27 ]. The extent to which it is involved in the induction of VLD needs further investigation.…”

“…A comparison of the VLD patterns between different Fitzpatrick phototypes might be interesting to assess the protective effect of melanin. Another clinically interesting finding was the initial occurrence of VLD after CPI [ 11 , 13 , 27 ]. When analysing VLD onset, we found that patients who were pre-treated with targeted therapy had a significantly later onset: the median time to VLD onset was 12.5 months in the kinase-inhibitor pre-treated group vs. 6.25 months in the group without prior targeted therapy.…”

“…The answer to the question of whether VLD patients without additional irAEs have a better treatment response in comparison to VLD patients with other irAEs was negative in our study population. Meanwhile, previous studies have indicated that melanoma patients who develop VLD have a better therapeutic response to immunotherapy [ 10 , 12 , 27 , 33 , 34 ]. A higher percentage of BSA affected by VLD and trend of expansion have previously been suggested as predictive markers for prolonged survival under CPI [ 36 ].…”

miR-148a-3pinhibits osteogenesis by targetingItga11via PI3K/Akt/GSK3/β-catenin pathway

“…Itga11 has also been reported to be involved in PI3K/Akt and Wnt signaling pathway, supporting our findings from another view. ITGA11 is one of the core genes that could influence PI3K/Akt signaling pathway once they were activated 28 , its expression can affect tumor progression by modulating the PI3K/Akt pathway 29 . Besides, Wnt pathway can be activated by osteolectin/α11β1 signaling 27 .…”

A comprehensive analysis of potential gastric cancer prognostic biomarker ITGBL1 associated with immune infiltration and epithelial–mesenchymal transition

“…Integrin ITGB3 interacted with heparan sulfate proteoglycans (HSPGs) and assisted in integrin endocytosis, promoting the metastasis of breast cancer [ 7 ]. In GC, integrin subunit alpha 11 promoted gastric cancer cell proliferation and invasion and inhibited apoptosis through the phosphatidylinositol 3-kinase/Akt pathway [ 8 ]. Integrin, beta-like 1 (ITGBL1), also called ten β Integrin EGF-like repeat domains (TIED), encodes beta integrin-related extracellular matrix protein, which is highly similar to integrin β subunits.…”