RUNX2 prompts triple negative breast cancer drug resistance through TGF-β pathway regulating breast cancer stem cells

Sep 21, 2026

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Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, and current care relies on cytotoxic agents such as epirubicin or paclitaxel. Acquired chemoresistance often drives tumor recurrence and metastasis, while the transcription factor RUNX2 has been implicated in tumor progression. Although RUNX2 may connect to TGF-β signaling, the exact molecular mechanism in TNBC chemoresistance is unclear. Multimodal in vitro and in vivo experiments show RUNX2 regulates chemoresistance by controlling cancer stem cell stemness via direct binding to TGF-β, with TGF-β also dual-regulating RUNX2 expression.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

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Introduction

Triple-negative breast cancer and chemotherapy challenge

Residual tumor cell changes: EMT and cancer stem cell stemness

TGF-β in cancer stem cells and chemoresistance

RUNX2 as a candidate regulator and link to TGF-β

Study objective: mechanisms of RUNX2 and TGF-β in TNBC chemoresistance

Neoplasia 48 (2024) 100967 Contents lists available at ScienceDirect Neoplasia journal [homepage:](homepage: www.elsevier.com/locate/neo)[ www.elsevier.com/locate/neo](homepage: www.elsevier.com/locate/neo) | RUNX2 prompts triple negative breast cancer drug resistance through TGF-β pathway regulating breast cancer stem cells
Fengxu Lva, 1, Wentao Sia, 1, Xiaodan Xu b, Xiaogang He c, Ying Wang a, Yetian Lid, *, Feifei Lia, * a Department of Pathophysiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, PR China.
b Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, PR China c Medical Faculty Mannheim, University of Heidelberg, Mannheim, 68169, Germany
d Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, PR China | | | | | --- | --- | --- | --- | | A R T I C L E I N F O | | A B S T R A C T | | | Keywords:
Triple negative breast cancer Chemoresistance
Cancer stem cells
RUNX2
TGF-β | | Triple-negative breast cancer (TNBC) stands out as the most aggressive subtype within the spectrum of breast cancer. The current clinical guidelines propose treatment strategies involving cytotoxic agents like epirubicin or paclitaxel. However, the emergence of acquired resistance frequently precipitates secondary tumor recurrence orthe spread of metastasis. In recent times, significant attention has been directed toward the transcription factor RUNX2, due to its pivotal role in both tumorigenesis and the progression of cancer. Previous researches suggest that RUNX2 might be intricately linked to the development of resistance against chemotherapy, with its mechanism of action possibly intertwined with the signaling of TGF-β. Nevertheless, the precise interplay between their effects and the exact molecular mechanisms underpinning chemoresistance in TNBC remain elusive. Therefore, we have taken a multifaceted approach from in vitro and in vivo experiments to validate the relationship between RUNX2 and TGF-β and to search for their pathogenic mechanisms in chemoresistance. In conclusion, we found that RUNX2 affects chemoresistance by regulating cancer cell stemness through direct binding to TGF-β, and that TGF-β dually regulates RUNX2 expression. The important finding will provide a new reference for clinical reversal of the development of chemoresistance in breast cancer. | | Introduction Breast cancer is one of the most common malignant tumors in women, profoundly impacting women’s quality of life and health [1]. Among highly heterogeneous breast cancers, triple negative breast cancer (TNBC), which is negative for estrogen receptor, progesterone receptor, and HER-2, is considered to be the most dangerous among all types of breast cancers, and predominantly affects young female patients [2,3]. Since TNBC lacks a clear therapeutic target and there is no clearly recommended targeted drug so far, chemotherapy is still the main treatment for TNBC, and clinical guidelines mostly recommend the use of cytotoxic drugs to kill cells, such as the anthracycline drug epirubicinor the paclitaxel [4]. However, more than 50 % of patients may experience tumor recurrence within 3 to 5 years after treatment, mainly due to acquired chemoresistance leading to secondary recurrence or metastasis [5]. Therefore, it is of great clinical significance to explore the resistance mechanism of TNBC to find the corresponding target to reverse the chemoresistance of TNBC. Many studies have shown that some residual tumor cells develop phenotypic changes in response to chemotherapeutic agents that lead to drug resistance, which is most commonly seen in epithelial mesenchymal transition (EMT) and cancer stem cell CSC-like stemness transition [6–8]. This process involves alterations in several signaling pathways. Among them, TGF-β related signaling pathways have attracted much attention [9,10]. In recent years, studies ha

FAQs

Why is chemoresistance a major problem in triple-negative breast cancer (TNBC)?

TNBC patients often develop acquired chemoresistance after cytotoxic treatment, leading to secondary recurrence and metastasis within a few years.

What role is proposed for RUNX2 in TNBC chemoresistance?

RUNX2 is suggested to contribute to chemoresistance by regulating cancer cell stemness and linking to TGF-β-related signaling pathways.

What relationship between RUNX2 and TGF-β is reported by the study?

RUNX2 affects chemoresistance by regulating stemness through direct binding to TGF-β, and TGF-β also dual-regulates RUNX2 expression.

Sep 21, 2026

Uploaded by Logic