2026-10-07T09:28:20Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34003032 2026-09-27T03:35:46Z category_24784 item_type_3 month_year_09_2026

<b>MLF2 Stabilizes KLF5 by Limiting FBXW7-Mediated Ubiquitination to Sustain PI3K/AKT Signaling in Gastric Cancer</b> Lianlei Yang (25114486) Cancer genetics Gastric cancer cell line <p dir="ltr">Gastric cancer (GC) remains a major cause of cancer-related mortality, and the mechanisms that preserve oncogenic protein stability remain incompletely understood. Here, we identify myeloid leukemia factor 2 (MLF2) as an oncogenic proteostatic regulator that protects KLF5 from ubiquitin-dependent degradation in GC. Analysis of TCGA datasets showed that MLF2 was upregulated in GC tissues and exhibited moderate discriminatory ability for distinguishing tumor from normal tissues. Survival analysis further indicated that low MLF2 expression was associated with favorable overall and disease-specific survival in patients with early-stage and node-negative disease. Functionally, MLF2 knockdown suppressed GC cell proliferation, colony formation, migration, and the growth of subcutaneous HGC27 xenografts in male BALB/c nude mice. Quantitative proteomic profiling identified PI3K/AKT signaling as a downstream pathway suppressed by MLF2 depletion, and KLF5 restoration partially rescued PI3K/AKT activation and malignant phenotypes in MLF2-deficient cells. Mechanistically, MLF2 maintained KLF5 protein abundance without altering KLF5 mRNA levels. MLF2 interacted with KLF5, reduced FBXW7 recruitment, and attenuated KLF5 ubiquitination and proteasomal degradation. Further analyses showed that MLF2 and FBXW7 bound overlapping or adjacent regions of KLF5, whereas AKT activation, GSK3β inhibition, FBXW7 knockdown, or KLF5-S303A mutation stabilized KLF5 after MLF2 depletion. These findings define the MLF2-KLF5-FBXW7 axis as a previously unrecognized proteostatic mechanism and suggest a potential therapeutic vulnerability in GC.</p> 2026-09-27T03:35:46Z Dataset Dataset 10.6084/m9.figshare.34003032.v1 https://figshare.com/articles/dataset/_b_MLF2_Stabilizes_KLF5_by_Limiting_FBXW7-Mediated_Ubiquitination_to_Sustain_PI3K_AKT_Signaling_in_Gastric_Cancer_b_/34003032 CC BY 4.0