Deficiency of Functional Iron-Sulfur Domains in ABCE1 Inhibits the Proliferation and Migration of Lung Adenocarcinomas By Regulating the Biogenesis of Beta-Actin In Vitro

Abstract

Background/Aims: ATP-binding cassette transporter E1 (ABCE1), a unique ABC superfamily member that bears two Fe-S clusters, is essential for metastatic progression in lung cancer. Fe-S clusters within ABCE1 are crucial for ribosome dissociation and translation reinitiation; however, whether these clusters promote tumor proliferation and migration is unclear. Methods: The interaction between ABCE1 and β-actin was confirmed using GST pull-down. The lung adenocarcinoma (LUAD) cell line A549 was transduced with lentiviral packaging vectors overexpressing either wild-type ABCE1 or ABCE1 with Fe-S cluster deletions (ΔABCE1). The role of Fe-S clusters in the viability and migration of cancer cells was evaluated using clonogenic, MTT, Transwell and wound healing assays. Cytoskeletal rearrangement was determined using immunofluorescent techniques. Results: Fe-S clusters were the key domains in ABCE1 involved in binding to β-actin. The proliferative and migratory capacity increased in cells overexpressing ABCE1. However, the absence of Fe-S clusters reversed these effects. A549 cells overexpressing ABCE1 exhibited irregular morphology and increased levels of cytoskeletal polymerization as indicated by the immunofluorescence images. In contrast, cells expressing the Fe-S cluster deletion mutant presented opposing effects. Conclusion: These results demonstrate the indispensable role of Fe-S clusters when ABCE1 participates in the proliferation and migration of LUADs by interacting with β-actin. The Fe-S clusters of ABCE1 may be potential targets for the prevention of lung cancer metastasis.

ATP‐binding cassette (ABC) transporters in cancer: A review of recent updates

“…Han et al conducted coimmunoprecipitation to reveal that ABCE1 formed complexes with β‐actin in vivo 142 . Subsequently, Yu et al found that the overexpression of ABCE1 could promote cell proliferation and migration in human lung adenocarcinoma A549 cell models via the interaction of Fe/S domains with β‐actin, while the absence of Fe/S domains in ABCE1 protein could have opposing activity through cytoskeleton rearrangement 143 . Overall, many researchers indicated that Fe/S domains in ABCE1 protein may be a promising therapeutic target for lung adenocarcinomas.…”

The expression and correlation between chemokine CCL7 and ABCE1 in non‑small cell lung cancer

“…In AC, the expression level of ABCE1 protein were higher than that in the squamous carcinoma. Recently, a series of studies revealed that ABCE1 may be a new interaction protein for β-actin and that the binding of ABCE1 to β-actin requires the Fe-S cluster domain (14,15). These results show that ABCE1 is highly expressed in many malignant tumor cells, indicating that this protein is closely related to the proliferation, invasion and metastasis of lung cancer.…”