What question did this study set out to answer?

This study investigates the roles of ATP7A and LIAS in the progression of lung adenocarcinoma and their relationship with cuproptosis.

April 18, 2026Cancer Cell International0 citationsOpen Access

ATP7A and LIAS promote lung adenocarcinoma progression through regulation of cuproptosis

WLWenzhou LiuSun Yat-sen University FLFei-Hai LiangGuangxi Medical University 冯冯俭Soochow University

Puntos clave

This study investigates the roles of ATP7A and LIAS in the progression of lung adenocarcinoma and their relationship with cuproptosis.
Analyzed ATP7A and LIAS expression in LUAD tissues and cell lines using RT-qPCR and western blotting.
Performed gain- and loss-of-function experiments to assess cell proliferation, migration, and EMT.
Evaluated cuproptosis-related changes through FDX1 expression and metabolic profiling.
Utilized nude mouse xenograft models for in vivo validation of findings.
ATP7A and LIAS were upregulated in LUAD samples, linked to poorer differentiation and advanced TNM stages.
Knockdown of ATP7A or LIAS inhibited LUAD cell proliferation and migration, and altered EMT.
Depletion of ATP7A or LIAS led to increased FDX1 expression and metabolic changes indicative of cuproptosis.
In vivo experiments showed that ATP7A or LIAS knockdown reduced tumor growth and increased apoptosis markers.

Resumen

Cuproptosis has been implicated in lung adenocarcinoma (LUAD), but whether it contributes to the biological functions of ATPase copper transporting alpha (ATP7A) and lipoic acid synthetase (LIAS) remains unclear. This study aimed to investigate the roles of ATP7A and LIAS in LUAD progression and their association with cuproptosis-related alterations. ATP7A and LIAS expression was assessed in LUAD-related human tissues (n = 20 per group) and LUAD cell lines (A549 and PC9) by RT-qPCR, western blotting, and immunohistochemistry. Gain- and loss-of-function experiments were used to evaluate cell proliferation, migration, and epithelial–mesenchymal transition (EMT) (CCK-8, wound-healing, and Transwell assays, with molecular analyses). Cuproptosis-related changes were assessed using FDX1 expression, pyruvate and α-ketoglutarate levels, mitochondrial ultrastructure, and lipoylation-related readouts. Nude mouse subcutaneous xenografts were used for in vivo validation, with an additional independent cohort for Ki-67 immunohistochemistry and TUNEL staining. ATP7A and LIAS were significantly upregulated in LUAD tissues and cell lines compared with controls (all p 0.05). In vivo, ATP7A or LIAS knockdown suppressed xenograft tumor growth (p < 0.01), with reduced Ki-67 staining and increased TUNEL positivity in the independent validation cohort (both p < 0.01). ATP7A and LIAS promote LUAD progression and are associated with cuproptosis-related alterations, supporting a role for ATP7A/LIAS-regulated cuproptosis-related pathways in LUAD.

Preguntar a la IA

Me gusta

Guardar

Ver artículo completo