Knockdown of DNAJC12 slows tumor progression and affects tumor radiosensitivity in esophageal squamous cell carcinoma

Purpose: To look into the influence of DNAJC12 knockdown on the progression and radio-sensitivity of esophageal squamous cell carcinoma (ESCC), with a focus on cellular mechanics and tumor microenvironment interactions. Methods: The TCGA database combined with immunohistochemical staining was used to validate the DNAJC12 expression in ESCC patients from the perspective of the clinic. DNAJC12 knockdown was performed in TE-1 and KYSE-150 cell lines to assess changes in proliferation, migration, invasion, apoptosis, and cellular mechanical properties (e.g., stiffness, adhesion, and contractility). The downstream molecule regulated by DNAJC12 was explored using Western blotting and biomechanical assays. The effect of DNAJC12 knockdown on tumor radiosensitivity was evaluated in vivo, with a focus on tumor stiffness and extracellular matrix (ECM) remodeling under irradiated conditions. Results: Upon analyzing the TCGA database and examining tumor tissue samples from patients, it was discovered that DNAJC12 exhibited high expression levels in tissues of ESCC. Vitro experiments showed that DNAJC12 knockdown significantly decreased cellular proliferation and migration (P < 0.05). Biomechanical assays revealed that DNAJC12 knockdown decreased cellular stiffness and contractility, suggesting a role in regulating cytoskeletal dynamics. Molecular analysis showed downregulation of P-ERK, MMP-2, N-Cadherin, P-P38, Snail, Vimentin, β-Catenin, Fibronectin, and Twist alongside upregulation of E-Cadherin (P < 0.05). Overexpression of SNAI1 could restore the proliferative and migratory capabilities of cells with downregulated DNAJC12. In vivo experiments, knockdown of DNAJC12 resulted in faster tumor growth under irradiated conditions (P < 0.05). Conclusion: DNAJC12 knockdown slows ESCC progression by modulating cellular biomechanical properties and molecular pathways. However, it enhances tumor growth post-radiotherapy, potentially due to altered mechanosensitive signaling and ECM remodeling. These findings highlight the interplay between molecular biology and biomechanics in ESCC progression and treatment response.