NPJ breast cancerOct 1, 2025

How TRIM39 helps triple-negative breast cancer avoid cell death by increasing RNF168

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

The TRIM39-RNF168 axis appears to help triple-negative breast cancer cells evade -linked .

Evidence

Preclinical TNBC cell and in vivo model experiments showed that high TRIM39 supported ferroptosis resistance, while knocking down TRIM39 or RNF168 activated autophagy-coupled ferroptosis and suppressed TNBC progression.

Caveat

The abstract reports model-system data only, so therapeutic relevance in patients and the safety of targeting this axis remain untested.

Simplified

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and due to the lack of robust therapeutic targets, treatment options remain limited to conventional cytotoxic chemotherapy and surgical resection. , a lysosome-dependent degradation process, is typically regarded as a survival mechanism. However, excessive degradation of ferritin may indirectly lead to Fe²⁺ accumulation, thereby facilitating . In this study, we reveal for the first time the existence of a TRIM39-RNF168 ubiquitination axis in the TNBC model that targets autophagy-dependent ferroptosis in TNBC cells. The high expression of TRIM39 in TNBC cells confers resistance to ferroptosis and enhances cell survival. Regulation of the TRIM39-RNF168 axis, achieved by knocking down TRIM39 or RNF168, can activate autophagy-coupled ferroptosis in TNBC cells. The activated autophagy-ferroptosis pathway effectively suppresses TNBC progression in vivo, presenting a promising potential therapeutic approach.

Key numbers

significantly reduced

Decrease in Cell Viability

Cell viability of cells after knockdown

higher ROS levels

Increased Markers

Reactive oxygen species (ROS) levels in knockdown cells

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Funding

Competing interests

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0 of 4

authors report competing interests

4 report none

PubMed

How TRIM39 helps triple-negative breast cancer avoid cell death by increasing RNF168

Abstract

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Abstract

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