TRIB3 promotes lipid accumulation and lipogenesis in esophageal cancer progression

Esophageal cancer is a malignant tumor with extremely poor prognosis. Its developmental mechanisms remain incompletely elucidated. Altered lipogenesis plays a crucial role in tumor progression. However, the specific mechanisms by which TRIB3 regulates lipid accumulation in esophageal cancer remain unclear. This study aims to investigate how TRIB3-ATF4 interaction influences lipogenic enzyme expression and tumor progression through the ERK1/2 pathway in esophageal cancer.

This study employed the esophageal cancer cell lines (TE5 and KYSE150) as a research model. We performed TRIB3 overexpression, knockdown, and ATF4 interaction analyses. These were combined with molecular biology techniques and functional assays (EdU, colony formation, migration, and invasion). Pharmacological inhibitors of ERK and FASN, alongside oleic acid (OA) rescue, validated the signaling and metabolic pathways.

TRIB3 regulates fatty acid metabolism. TRIB3 knockdown suppresses fatty acid biosynthesis, cell growth, and migration. Mechanistically, TRIB3 interacts with ATF4 to activate the MEK/ERK pathway. FASN inhibition reverses TRIB3's oncogenic effects. Conversely, OA rescues the tumor-suppressive phenotypes of TRIB3 knockdown. Inhibition of the MEK/ERK pathway attenuates TRIB3-mediated lipid metabolism and progression.

This study identifies TRIB3 as a key metabolic regulator in esophageal cancer. It links stress adaptation to lipogenic reprogramming. Targeting this metabolic vulnerability represents a promising therapeutic strategy.