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Updated: Aug 5, 2026

Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel
Published on: May 14, 2018
VASN Enhances IGF2BP3 Stability via USP10 Deubiquitination to Promote Triple-negative Breast Cancer Paclitaxel
Hao Liu1, Zexiu Lu2, Maoshan Chen1
1Department of Breast and Thyroid Surgery, Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
None:
Triple-negative breast cancer (TNBC) is an aggressive subtype lacking effective treatment options, and paclitaxel resistance remains a major clinical challenge. This study investigated the role of VASN in mediating paclitaxel resistance in TNBC by integrating transcriptomic and single-cell RNA sequencing data from public databases and clinical samples. Using paclitaxel-resistant TNBC cell lines (MDA-MB-231R and CAL-51R) and xenograft models, we revealed that VASN was significantly upregulated in resistant TNBC cells and tissues, correlating with poor prognosis. Mechanistically, CEBPB directly bound to the VASN promoter to activate its transcription, and VASN interacted with IGF2BP3 via its LRR domain, recruiting USP10 to deubiquitinate and stabilize IGF2BP3 by suppressing K48-linked polyubiquitination. Stabilized IGF2BP3 enhanced ABCB1 expression through m6A-dependent mRNA stabilization, activating the PI3K/AKT pathway and driving paclitaxel resistance. Genetic or pharmacological inhibition of VASN resensitized resistant cells to paclitaxel, and computational drug screening identified Trametinib as a candidate to downregulate VASN. Trametinib synergized with paclitaxel to effectively suppress tumor growth without obvious toxicity in resistant models. In summary, we uncovered a new CEBPB-VASN/IGF2BP3/USP10-ABCB1 axis responsible for paclitaxel resistance in TNBC. Targeting VASN with Trametinib in combination with paclitaxel represents a promising therapeutic strategy to overcome chemoresistance, offering a rationale for precision medicine in resistant TNBC.
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