Role of Integrin β1 in the progression and chemo-resistance of esophageal squamous cell carcinoma

Objective: Integrins have been shown to play an important role in the tumorigenesis of many cancers. In this work, we aimed to explore the expression and clinical value of Integrin alpha 5 beta 1 in esophageal squamous cell carcinoma (ESCC), and the effect of integrin beta 1 on the development and chemo-resistance of ESCC cells. Methods: The expression profiling of integrins was analyzed in the mRNA expression dataset of ESCC. The expression of Integrin alpha 5 beta 1 in 278 cases of ESCC tissues and 62 cases of paracancerous tissues was detected by immunohistochemistry (IHC). The association between the expression of Integrin alpha 5 beta 1 and the survival of ESCC patients was analyzed by Kaplan-Meier analysis. The effect of Integrin beta 1 on the proliferation, migration, and invasion of ESCC cells was examined by MTS, Transwell migration, and Transwell invasion assay. The effect of Integrin beta 1 and L1 cell adhesion molecule (L1CAM) on cisplatin resistance was detected by MTS and the signal pathways involved were analyzed by Western blotting. Results: Integrin beta 1 and Integrin alpha 5 were significantly up-regulated in ESCC. High expression of Integrin beta 1 was also related to worse overall survival of ESCC patients and patients with low levels of both Integrin beta 1 and Integrin alpha 5 showed the shortest survival. Results of IHC revealed that Integrin alpha 5 beta 1 was up-regulated in ESCC and its high expression was associated with poor prognosis and could serve as an independent prognostic factor. siRNA-mediated Integrin beta 1 silencing or antibody blocking restrained the proliferation, migration, and invasion of ESCC cells. Simultaneous knockdown of Integrin beta 1 and L1CAM reduced the cisplatin resistance of ESCC cells. Further studies showed that knockdown of Integrin beta 1 and L1CAM suppressed the activity of Akt signaling with or without cisplatin treatment. Moreover, dual high expression of Integrin beta 1 and L1CAM was related to worse overall survival of ESCC patients treated with preoperative chemotherapy. Conclusion: Integrin alpha 5 beta 1 was up-regulated in ESCC and could be used as a new prognostic indicator for ESCC patients. In addition, Integrin beta 1 was involved in the proliferation, invasion, and chemo-resistance of ESCC cells.

Automated summary

This study found that Integrin alpha 5 beta 1 is up-regulated in esophageal squamous cell carcinoma (ESCC) and is associated with prognosis. Knockdown of Integrin beta 1 and L1CAM can inhibit the proliferation, migration, and invasion of ESCC cells and reduce cisplatin resistance. These findings suggest that Integrin alpha 5 beta 1 and beta 1 play important roles in the development and chemo-resistance of ESCC.