Functional Role of FUNDC1 in ESCC Progression via Modulation of Mitochondrial Fission and HMGB1/PI3K/Akt Signalling

This study investigates the functional role of FUNDC1 in the progression of esophageal squamous cell carcinoma (ESCC). Transcriptomic analysis using the Cancer Genome Atlas (TCGA) dataset revealed that FUNDC1 is significantly overexpressed in ESCC tissues and is associated with unfavourable patient prognosis. In vitro assays demonstrated that silencing FUNDC1 suppresses ESCC cell proliferation, migration, and invasion. Mechanistically, FUNDC1 knockdown was found to be associated with mitochondrial morphologic features suggestive of reduced fission and inhibits the epithelial-mesenchymal transition (EMT) process, both of which are critical for tumour metastasis. Further investigation revealed that FUNDC1 modulates EMT through the HMGB1/PI3K/Akt signaling pathway. Collectively, these findings indicate that FUNDC1 contributes to ESCC progression by regulating mitochondrial dynamics and EMT. Thus, FUNDC1 may represent a mechanistically relevant factor in ESCC progression and warrants further investigation as a therapeutic target. To this end, further studies involving clinical validation, in vivo models, and pharmacological inhibition are warranted to fully explore the therapeutic implications of targeting FUNDC1 in ESCC.