YB-1 drives triple-negative breast cancer progression and paclitaxel resistance through Wnt/β-catenin pathway

Sep 23, 2026

Triple-negative breast cancer (TNBC) remains highly aggressive and heterogeneous, with drug resistance to chemotherapy often driving poor clinical outcomes. Y-box binding protein-1 (YB-1) is implicated in cancer progression and resistance, yet its TNBC-specific mechanisms are unclear. Tumor and adjacent normal tissues from 10 TNBC patients and TNBC cell experiments assessed YB-1 expression, viability, proliferation, apoptosis, and Wnt/β-catenin signaling, alongside in vivo xenograft testing. Results show YB-1 overexpression enhances proliferation, suppresses apoptosis, and increases paclitaxel resistance via Wnt/β-catenin activation, reversed by YB-1 suppression, supporting YB-1 as a therapeutic target.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Introduction

TNBC background and paclitaxel resistance

YB-1 functions and rationale

Study outcomes (from abstract)

YB-1 expression in TNBC

Effects on proliferation, apoptosis, and paclitaxel sensitivity

Wnt/β-catenin pathway mechanism

In vivo validation and therapeutic implication

Naunyn-Schmiedeberg's Archives of Pharmacology (2026) 399:13497–13512 [https://doi.org/10.1007/s00210-026-05146-7](https://doi.org/10.1007/s00210-026-05146-7) YB‑1 drives triple‑negative breast cancer progression and paclitaxel resistance through Wnt/β‑catenin pathway Yuan Cao1 · Zhiqiang Peng2 · Tenghua Yu3 · Hanzhi Dong1 Received: 24 September 2025 / Accepted: 20 February 2026 / Published online: 27 March 2026 © The Author(s) 2026 Abstract Triple-negative breast cancer (TNBC) is a highly aggressive and heterogeneous subtype of breast cancer. While chemotherapy remains the cornerstone ofTNBC treatment, the frequent development of drug resistance often results in unfavorable clinical outcomes. Y-box binding protein-1 (YB-1) has been implicated in cancer progression and drug resistance, but its specific role and mechanisms in TNBC are poorly understood. This study investigates the impact of YB-1 on TNBC progression and paclitaxel resistance. Tumor and adjacent normal tissues were collected from 10 patients with TNBC to evaluate YB-1 expression. Cell viability, proliferation, and apoptosis were assessed using the CCK-8 assay, EdU staining, and flow cytometry, respectively. A xenograft model was employed to monitor tumor growth, while protein levels were analyzed using western blotting and immunohistochemistry. Elevated YB-1 expression was observed in TNBC tissues and cells. Functional assays revealed that YB-1 overexpression enhanced TNBC cell proliferation, inhibited apoptosis, and heightened resistance to paclitaxel in vitro. Conversely, YB-1 suppression yielded the opposite effects. Mechanistically, YB-1 overexpression was associated with enhanced Wnt/β-catenin pathway activity, which functionally contributed to increased paclitaxel resistance. Similar effects were confirmed in vivo, where YB-1 overexpression accelerated tumor growth, increased paclitaxel resistance, and activated the Wnt/β-catenin pathway, whereas YB-1 suppression reversed these outcomes. In conclusion, YB-1 facilitates TNBC cell proliferation, suppresses apoptosis, and strengthens paclitaxel resistance through activation of the Wnt/β-catenin pathway. These findings highlight YB-1 as a promising therapeutic target for TNBC treatment. Keywords TNBC · YB-1 · Paclitaxel · Wnt/β-catenin pathway · Drug resistance Abbreviations CSC Cancer stem cell EMT Epithelial-to-mesenchymal transition ER Estrogen receptor PR Progesterone receptor SD Standard deviation TNBC Triple-negative breast cancer * Hanzhi Dong [ndzhlyy1394@ncu.edu.cn](ndzhlyy1394@ncu.edu.cn) 1 Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17, Yongwai Zheng Street, Donghu District, Nanchang 330000, China 2 Department of Lymphohematology, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang 330029, China 3 Department of Breast Surgery, Jiangxi Clinical Research Center for Cancer, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang 330029, China BCRP Breast cancer resistance protein MRP2 Multidrug resistance-associated protein 2 P-gp P-glycoprotein; PTX, Paclitaxel Introduction Breast cancer ranks as the leading cancer in women globally, with a morbidity rate of 24.5% and mortality of 15.5%(Sung et al. 2021a) . Triple-negative breast cancer (TNBC), a subtype accounting for approximately 15% of cases, is defined by the absence of estrogen (ER) and progesterone (PR) receptor and HER2 expression (Ensenyat-Mendez et al. 2021 ; Bou Zerdan et al. 2022a) . TNBC is characterized by its heterogeneity and aggressiveness, leading to the poorest prognosis among breast cancer subtypes. Approximately 30–40% of patients with TNBC develop distant metastases, resulting in poor clinical outcomes (Mahmoud et al. 2022 ; Cao et al. 2024) . Currently, chemotherapy remains the primary treatment for TNBC, with paclitaxel being a widely used first-lin

FAQs

What role does YB-1 play in TNBC progression and paclitaxel resistance?

YB-1 overexpression enhances TNBC cell proliferation, inhibits apoptosis, and increases resistance to paclitaxel, while YB-1 suppression produces opposite effects. The abstract also links these changes to TNBC tumor growth in vivo.

How was YB-1 expression and function evaluated in the study?

Tumor and adjacent normal tissues were collected from 10 TNBC patients to assess YB-1 expression. Functional assays used CCK-8, EdU staining, and flow cytometry, with western blotting and immunohistochemistry for protein analysis.

Which signaling pathway mediates the paclitaxel resistance driven by YB-1?

The study reports that YB-1 overexpression is associated with increased Wnt/β-catenin pathway activity, which functionally contributes to higher paclitaxel resistance. In vivo results confirm activation of Wnt/β-catenin alongside accelerated tumor growth.

Sep 23, 2026

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