What question did this study set out to answer?

To investigate the role of ESM1 in bevacizumab resistance in ovarian cancer and identify its regulatory mechanisms.

February 9, 2026Open Access

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

Key Points

To investigate the role of ESM1 in bevacizumab resistance in ovarian cancer and identify its regulatory mechanisms.
Identified ESM1 as a key gene in bevacizumab-resistant ovarian cancer through gene expression analyses.
Examined the impact of ESM1 on the ITGB1/FAK axis and angiogenesis in cancer cell lines and mouse models.
Studied the regulatory effect of TRIM28 on ESM1 SUMOylation and stability.
ESM1 was found to promote bevacizumab resistance and tumor growth in various cancer models.
TRIM28 enhances ESM1 stability via SUMOylation, leading to increased angiogenesis and bevacizumab resistance in mice.
The ITGB1/FAK signaling pathway was activated by ESM1, implicating it in neovascularization and drug resistance.

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.

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Cite This Study

Ran et al. (Sun,) studied this question.

synapsesocial.com/papers/698978dff0ec2af6756e7175 https://doi.org/https://doi.org/10.1016/j.celrep.2026.116927

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