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Volume 26
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10.3390/ijms262412183
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Ring-Finger Protein 126 (RNF126) Promotes Anoikis Resistance and Peritoneal Colonization in Ovarian Cancer

by
Anh Duc Vu
1,†,
Shiori Mori
1,†,
Kanako Akamatsu
1,
Jun Nakayama
2 and
Takeharu Sakamoto
1,*
1
Department of Cancer Biology, Institute of Biomedical Science, Kansai Medical University, Osaka 573-1010, Japan
2
Department of Oncogenesis and Growth Regulation, Research Institute, Osaka International Cancer Institute, Osaka 541-8567, Japan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2025, 26(24), 12183; https://doi.org/10.3390/ijms262412183
Submission received: 18 November 2025 / Revised: 11 December 2025 / Accepted: 17 December 2025 / Published: 18 December 2025
(This article belongs to the Special Issue Molecular Biology of Cancer—Implications for Diagnosis and Treatment: 3rd Edition)
Review Reports Versions Notes

Abstract

Ovarian cancer (OC) represents the most lethal gynecologic malignancy because the majority of patients with OC are diagnosed at advanced stages with peritoneal colonization of OC cells owing to subtle and nonspecific nature of symptoms. Thus, peritoneal colonization-directed therapeutic approaches are urgently needed for patients with advanced OC. Here, we investigated whether Ring-finger protein 126 (RNF126), an E3 ubiquitin ligase that is aberrantly upregulated in epithelial OC tissues, contributes to the peritoneal colonization of OC. RNF126-depleted OC cells showed comparable proliferation under normal culture conditions but displayed decreased growth under floating (anchorage-independent) conditions in vitro. Further analyses showed that RNF126 promoted anoikis resistance in vitro and increased peritoneal colonization in immunodeficient mice in a RING domain-dependent manner. Mechanistically, RNF126 activated the transcriptional factor NF-κB in OC cells under floating conditions in a RING domain-dependent manner, and this NF-κB activation was essential for anchorage-independent growth and peritoneal colonization of OC cells. Thus, RNF126 is a possible target for the prevention and/or therapy of peritoneally colonized OC.
Keywords: anoikis; NF-κB; peritoneal dissemination; ovarian cancer; RNF126 anoikis; NF-κB; peritoneal dissemination; ovarian cancer; RNF126

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MDPI and ACS Style

Vu, A.D.; Mori, S.; Akamatsu, K.; Nakayama, J.; Sakamoto, T. Ring-Finger Protein 126 (RNF126) Promotes Anoikis Resistance and Peritoneal Colonization in Ovarian Cancer. Int. J. Mol. Sci. 2025, 26, 12183. https://doi.org/10.3390/ijms262412183

AMA Style

Vu AD, Mori S, Akamatsu K, Nakayama J, Sakamoto T. Ring-Finger Protein 126 (RNF126) Promotes Anoikis Resistance and Peritoneal Colonization in Ovarian Cancer. International Journal of Molecular Sciences. 2025; 26(24):12183. https://doi.org/10.3390/ijms262412183

Chicago/Turabian Style

Vu, Anh Duc, Shiori Mori, Kanako Akamatsu, Jun Nakayama, and Takeharu Sakamoto. 2025. "Ring-Finger Protein 126 (RNF126) Promotes Anoikis Resistance and Peritoneal Colonization in Ovarian Cancer" International Journal of Molecular Sciences 26, no. 24: 12183. https://doi.org/10.3390/ijms262412183

APA Style

Vu, A. D., Mori, S., Akamatsu, K., Nakayama, J., & Sakamoto, T. (2025). Ring-Finger Protein 126 (RNF126) Promotes Anoikis Resistance and Peritoneal Colonization in Ovarian Cancer. International Journal of Molecular Sciences, 26(24), 12183. https://doi.org/10.3390/ijms262412183

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