What does this research mean for the field?

TET1 counteracts the aggressiveness of triple-negative breast cancer (TNBC) by modulating glucose metabolism and immune responses under oncogenic stress. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To investigate the role of TET1 in glucose metabolism and aggressiveness of triple-negative breast cancer (TNBC) under oncogenic stress.

February 21, 2026

Abstract A034: TET1 Orchestrates Glucose Metabolism and Counteracts TNBC Aggressiveness under the Oncogenic stress

Key Points

To investigate the role of TET1 in glucose metabolism and aggressiveness of triple-negative breast cancer (TNBC) under oncogenic stress.
Examined the interplay between TET1, MCT-1, IL-6, and NF-κB in TNBC models.
Utilized RNA-sequencing and metabolomics to analyze metabolic changes.
Assessed the effects of TET1 overexpression and silencing on TNBC cell growth and motility.
TET1 overexpression reduces TNBC cell growth, motility, and stemness.
TET1 inversely correlates with MCT-1, IL-6, and NF-κB in metastatic breast cancer.
Depleted TET1 and induced MCT-1 worsen metastasis to lungs, liver, and bones.

Abstract

Abstract The role of epigenetic mechanisms in silencing tumor suppressor genes and promoting triple-negative breast cancer (TNBC) progression and metastasis remain unclear. Multiple Copies in T-cell malignancy 1 (MCT-1) also known as malignant T-cell-amplified sequence 1 (MCTS1) is an oncoprotein overexpressed in TNBC and invasive BC. Our new findings reveal that MCT-1 upregulates DNA methyltransferase 1 (DNMT1) and downregulates ten-eleven translocation methylcytosine dioxygenase 1 (TET1) via the interleukin-6 (IL-6)/nuclear factor kappa B (NF-κB) pathway, causing hypermethylation and suppression of the miR-34a gene promoter. Higher miR-34a and TET1 expression levels are correlated with better survival of BC patients. Overexpression of TET1 suppresses TNBC cell growth, motility, stemness, and M2 macrophage activity driven by the MCT-1 oncogenic activity. Conversely, silencing TET1 or using the selective inhibitor NSC-370284 exacerbates TNBC malignancies. Clinically, TET1 is inversely correlated with MCT-1, IL-6 and NF-κB but not with DNMT1 in metastatic breast cancer. TET1 and miR-34a both reduce MCT-1-promoted glucose uptake and lactate production. Consistently, RNA- sequencing and metabolomics analyses show that TET1 counters MCT-1 effects on inducing the glycolytic metabolites and metabolism profiling. Elevated TET1 levels efficiently limits primary TNBC growth and the postoperative metastasis, which MCT-1 otherwise promotes. Significantly, depleted TET1 and induced MCT-1 synergistically aggravate TNBC metastasis to the lungs, liver, and bones. Collectively, TET1 modulates aggressiveness, metabolism, and immunity of TNBC under the oncogenic stress. Citation Format: Pao-Pao Yang, Aushia Tanzih . Al Haq, Hong-Yu Tseng, Jou-Ho Shih, Li-Mei Chen, Michael P. Snyder, Hsin-Ling Hsu. TET1 Orchestrates Glucose Metabolism and Counteracts TNBC Aggressiveness under the Oncogenic stress abstract. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr A034.

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