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ACSL4 coordinates metabolic and cell cycle reprogramming to promote endometrial cancer progression
Hongtao Guo1, Yitong Ma2, Liangjian Ma2
1The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu 730000, China; Department of Obstetrics and Gynecology, the First Hospital of Lanzhou University, Gansu Provincial Clinical Research Center for Gynecological Oncology, Branch of National Clinical Research Center for Gynecology and Obstetrics, Lanzhou, Gansu 730000, China.
None:
Endometrial cancer (EC) is a common gynecologic malignancy associated with lipid metabolic reprogramming. We identified ACSL4, a fatty acid-activating enzyme, as significantly upregulated in EC and inversely correlated with tumor differentiation. Functional assays revealed that ACSL4 promotes EC cell proliferation, migration, and G1/S progression, while its knockdown exerts suppressive effects. Mechanistically, ACSL4 activates the PPARα-CPT1C axis to enhance fatty acid β-oxidation and upregulates E2F2 to drive cell cycle progression. Inhibition of ACSL4 with PRGL493 suppressed tumor growth in vitro and in vivo. These findings highlight ACSL4 as a dual regulator of lipid metabolism and cell proliferation and a potential therapeutic target in EC.
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