Transcription factor FOSL2 enhances glycolytic metabolism and metastatic progression in lung adenocarcinoma via activation of BZW1.

As a pivotal mode of energy metabolism, glycolysis has been extensively validated for its role in facilitating diverse malignant phenotypes, most notably tumor proliferation and metastatic dissemination. This study aimed at exploring the role of BZW1 in lung adenocarcinoma (LUAD) glycolysis and metastasis. In our study, LUAD samples were collected and LUAD cell line (A549 and H1975) were employed. Gene expression was detected by quantitative real-time PCR, western blotting and immunohistochemistry. Cell migration and invasion were detected by wound healing and Transwell assay. Glycolysis level was analyzed by biomarker expression, lactate level detection, ECAR (extracellular acidification rate) experiment, intracellular ATP level and glucose consumption measure. The molecular interaction between FOSL2 and BZW1 was confirmed by dual-luciferase reporter assay, chromatin immunoprecipitation assay-qPCR (CHIP-qPCR) and electrophoretic mobility shift assay (EMSA). Our results showed that BZW1 was upregulated in LUAD tissues, compared with paracancerous tissues. Overexpressing BZW1 promoted metastatic behavior and glycolysis activity. Conversely, BZW1 knockdown had an opposite effect. Moreover, FOSL2 was identified as a transcriptional activator of BZW1. FOSL2 overexpression enhanced cell migration, invasion and glycolysis, which were reversed by BZW1 knockdown. BZW1 was also confirmed to promote LUAD progression in xenograft tumor model. In summary, our finding demonstrated that FOSL2 promoted glycolysis and metastatic potential in lung adenocarcinoma cells by transcriptionally activating BZW1, which provided a novel mechanism driving LUAD progression and suggested FOSL2-BZW1 signaling as a potential therapeutic target for LUAD.