Knockdown of ABCB7 inhibits esophageal cancer progression by inhibiting the TGF-β/Smad signaling

Objectives: Esophageal Cancer accounts for the seventh in human cancers, and the sixth in the global Cancer death. ATP-binding cassette, sub-family B (MDR/TAP), member 7 (ABCB7) maintains intracellular iron homeostasis and involved in the regulation of tumor progression. However, the role and mechanism of ABCB7 in esophageal Cancer remained unclear.

Methods: Here, we investigated its role and regulatory mechanism by knocking down ABCB7 in Eca109 and KYSE30 cells.

Results: ABCB7 was significantly upregulated in esophageal Cancer tissues, and was strongly associated with metastasis and poor prognosis of patients. ABCB7 knockdown inhibits the proliferation, migration and invasion of esophageal Cancer cells. Importantly, ABCB7 knockdown induces Apoptosis and non-apoptotic cell death in flow cytometry analysis. Higher intracellular total iron concentration was observed in ABCB7 knockdown Eca109 and KYSE30 cells. We further analyzed ABCB7 expression related genes in esophageal Cancer tissues. COX7B were positively correlated with the expression of ABCB7 in 440 esophageal Cancer tissues. COX7B rescued the inhibition of cell proliferation and elevated total iron concentration induced by ABCB7 knockdown. In addition, Western blot results showed that ABCB7 knockdown reversed the epithelial-mesenchymal transition (EMT) process and inhibited the TGF-β signaling pathway in Eca109 and KYSE30 cells.

Conclusion: In conclusion, ABCB7 knockdown inhibits the TGF-β signaling pathway, inhibits the survival of esophageal Cancer cells by inducing cell death, and reverses the EMT process. Targeting ABCB7 or COX7B could be a novel strategy for the treatment of esophageal Cancer.

ATP-Binding cassette; Esophageal cancer; Ferroptosis; Prognosis; ROS; Sub-family B.