IntegrinB5 upregulated by HER2 in gastric cancer: a promising biomarker for liver metastasis

Background: Liver is the most frequent metastatic site of gastric cancer (GC), especially in patients with HER2 positive GC. Exosomal integrin alpha v beta 5 has been shown to promote liver metastasis (LM), and the cross talk between integrins and HER2 during breast cancer metastasis has been reported. However, whether there's an association between HER2 and integrin alpha v beta 5 (ITGAVB5), and whether their association has predictive value in GC liver metastasis (GCLM) remains unknown. Methods: The association between ITGB5 and HER2 were accessed by RT-PCR, western blot and ELISA. We tested the function of ITGB5 on HER2 positive GC cells using Transwell assays and scratch assays. Besides, we detect ITGB5 expression in tumor tissue of GC patients and exosomes derived from advanced GC to analyze the association between HER2 and LM. Results: In our study, we found that ITGB5, rather than ITGAV, was highly upregulated by HER2 through PI3K-AKT pathways in HER2 positive GC. Overexpression of ITGB5 promoted the migration and invasion of HER2 positive GC cells in vitro. ITGB5 was found to be an independent prognostic factor for GC. Besides, ITGB5 level was only associated with LM. Detection of exosomal ITGB5 and HER2 in the serum of GC patients revealed that exosomal ITGB5 and HER2 levels are in accordance with that in tissue, and exosomal ITGB5 level was higher in GCLM than other metastasis. Conclusions: Our study demonstrated ITGB5 is regulated and functions in accordance with HER2 in promoting GCLM. Exosomal ITGB5 levels might be a potential liquid biopsy biomarker for GCLM.