ESM1 SUMOylation mediates bevacizumab resistance in ovarian cancer through ITGB1-FAK-driven angiogenesis

Cell Reports 2026 Open access

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Authors: Xiaomin Ran, Juan Zhang, Juan Yang, Hui Li, Dan Liu, Xing Tang, Wenchao Zhou, Xueru Liu, Yukun Li, Bikang Yang
DOI: 10.1016/j.celrep.2026.116927
Cited by: 1
References: 82

Abstract

Bevacizumab (Bev) resistance limits therapeutic efficacy in ovarian cancer (OC) patients. We identified ESM1 as a key gene in Bev-resistant OC. ESM1 secreted by OC-resistant cell lines activates the ITGB1/FAK axis to induce neovascularization and Bev resistance. Additionally, ESM1 overexpression promoted the growth and Bev resistance of OC, lung, intestinal, and hepatocellular carcinoma tumors. Then, we identified TRIM28 as an upstream regulator that stabilizes ESM1 by promoting SUMOylation, inhibiting its proteasomal degradation. In OC mice, TRIM28 overexpression promotes angiogenesis and Bev resistance via ESM1-mediated ITGB1/FAK activation. This work unveils a new molecular pathway underlying Bev resistance in OC and proposes TRIM28 and ESM1 as potential therapeutic targets.

Fields of Study & Subjects

Inflammation biomarkers and pathways Inflammasome and immune disorders Apelin-related biomedical research

Publication details

Journal / source
Cell Reports
Publisher
Elsevier BV
Volume
45
Issue
2
Pages
116927–116927
Publication date
1 February 2026
Language
EN