SCARA5 induced ferroptosis to effect ESCC proliferation and metastasis by combining with Ferritin light chain

作者：Yan Liu, Rong Xiong, Ting Xiao, Li Xiong, Jialin Wu, Junfeng Li, Gang Feng, Guiqin Song, Kang Liu · 发表于：BMC Cancer · 年份：2022 · DOI：10.1186/s12885-022-10414-9 · 被引用次数：30 · 研究领域：Ferroptosis and cancer prognosis、Bone and Dental Protein Studies、Clusterin in disease pathology

Abstract Background Esophageal squamous cell carcinoma (ESCC) remains one of the most lethal cancers worldwide accompany with an extremely poor prognosis. Therefore, this study aims to screen for new molecules affecting ESCC and explore their mechanisms of action to provide ideas for targeted therapies for ESCC. Methods Firstly, we screened out the membrane protein SCARA5 by high-throughput sequencing of the ESCC patient tissues, and RT-qPCR and WB were used to verify the differential expression of SCARA5 in esophageal cell lines, and IHC analyzed the expression localization of SCARA5 in ESCC tissue. Then, flow cytometry, wound healing assay, Transwell assay and CCK-8 assay were used to explore the effects of SCARA5 on cell cycle, migration and invasion as well as cell proliferation activity of esophageal squamous carcinoma cells. Meanwhile, transmission electron microscopy was used to detect changes in cellular mitochondrial morphology, and flow cytometry were used to detect changes in intracellular reactive oxygen metabolism, and immunofluorescence and flow cytometry were used to detect changes in intracellular Fe 2+ . Mechanistically, co-immunoprecipitation was used to detect whether SCARA5 binds to ferritin light chain, and ferroptosis-related protein expression was detected by WB. Finally, the tumor xenograft model was applied to validation the role of SCARA5 tumor growth inhibition in vivo. Results We found that SCARA5 was aberrantly decreased in ESCC tissues and cell l...