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A Stem Cell-Osteogenesis Axis in Malignant Breast Calcification: SQLE-Driven Reprogramming of Adipose-Derived
Yue Wu1,2, Min Zhang3, Pengfei Li1,2
1The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, No. 22 Hankou Rd, Nanjing, 210093, PR China.
Stem Cell Reviews and Reports
|April 21, 2026
Summary
This study reveals SQLE drives malignant breast calcifications through stromal cell mineralization and mitochondrial dysfunction, challenging passive necrosis models. It highlights SQLE as a potential biomarker and therapeutic target for breast cancer.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Breast calcifications are key mammographic indicators for early breast cancer detection.
- While often viewed as passive deposits, calcifications may result from active tumor microenvironment remodeling, involving mesenchymal stem cells.
- Adipose-derived mesenchymal stem cells (ADSCs) have osteogenic potential, but their role in malignant calcification is unclear.
Purpose of the Study:
- To investigate the role of ADSCs in malignant breast calcification.
- To identify genes involved in the mineralization process of malignant breast calcifications.
- To explore the underlying mechanisms of ADSC-mediated calcification in breast cancer.
Main Methods:
- RNA sequencing of malignant and benign calcified breast tissues to identify differentially expressed genes.
- Validation of candidate genes using public datasets, immunohistochemistry, and survival analysis.
- Functional assays on genetically modified ADSCs (overexpressing SQLE or HGD) and in vivo xenograft models to assess osteogenic differentiation, mineralization, and tumor growth.
Main Results:
- SQLE was identified as a top upregulated gene in malignant calcifications, associated with poor survival and stromal cell expression.
- Overexpressed SQLE significantly enhanced ADSC osteogenic differentiation and matrix mineralization, promoting ectopic calcification in vivo.
- Mechanistically, SQLE induced mitochondrial dysfunction, impaired oxidative phosphorylation, and promoted mitochondrial calcium accumulation, leading to mineralization.
Conclusions:
- SQLE is a novel driver of stromal mineralization and malignant breast calcification through mitochondrial dysfunction and calcium dysregulation.
- These findings challenge the passive necrosis model, suggesting active stromal remodeling.
- SQLE represents a potential biomarker for malignant calcifications and a therapeutic target for breast cancer interventions.
