Sorting nexin 10 promotes triple-negative breast cancer progression through modulating cholesterol biosynthesis via stabilizing SREBP2.
- 1Clinical Medical Research Center, Institute of Cancer Research, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
- 2Department of Endocrinology and Metabolism, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
- 3Department of Metabolism and Endocrinology, the Second Affiliated Hospital of University of South China, Hengyang, Hunan, China.
Abstract
Objective
Triple-negative breast cancer (TNBC) lacks effective therapeutics in clinical practice. Sorting nexin 10 (SNX10) plays essential roles in various cancers, and the role of SNX10 in TNBC remains unknown. This study investigated the role and action mechanism of SNX10 in TNBC.Methods
Using the Kaplan-Meier Plotter database and bc-GenExMiner database to analyze the SNX10 expression and clinical significance. Functional assays, including MTT, colony formation, transwell assays, and xenograft experiments, were used to evaluate the role of SNX10 in TNBC. The GeneChip PrimeView Human Gene Expression Array was used to determine the downstream targets and pathways. Cholesterol levels and the expression of enriched cholesterol synthesis genes were detected by Filipin assay, RT-PCR, and Western Blot. The relationship of SNX10 and cholesterol biosynthesis was confirmed using CO-IP and immunofluorescence staining assays.Results
SNX10 is positively related to poor prognosis of breast cancer and markedly up-regulated in TNBC. Knockdown of SNX10 suppressed cell proliferation, migration, and invasion, and slowed the tumor growth in vivo. Mechanistically, SNX10 positively regulates the content and distribution of cellular cholesterol, as does the expression of enriched cholesterol synthesis genes, and SNX10 interacts with SREBP2 and prolongs its half-life. Blocking with lovastatin, cholesterol, or siSREBP2 reversed these effects caused by altering SNX10 in TNBC cells in vitro.Conclusion
SNX10 promoted TNBC progression through the regulation of cholesterol biosynthesis, which was mediated by interaction with SREBP2 and maintenance of its stability. SNX10 may be an effective therapeutic target for TNBC, and our study provides new insights into therapeutic strategies.
Related
- MSRB3 promotes gastric cancer progression and immunotherapy resistance by stabilizing GPX4 to inhibit ferroptosis
- AMOT mediates YAP1 activation and promotes the cell progression and glycolysis in non-small cell lung cancer by modulating the Hippo signaling pathway
- m6A-Driven Intratumoral Cholesterol Biosynthesis Fuels Castration-Resistant Prostate Cancer Progression
- VCP-Regulated LMF2 Stabilizes the Cholesterol Biosynthesis Enzyme HMGCS1 to Drive Cancer Progression and Confer Capecitabine Resistance in Triple-Negative Breast Cancer.
- Matrix stiffness promotes colorectal cancer progression via Golgi-dependent cholesterol synthesis.
BibTeX
@article{guo2026sorting,
title = {{Sorting nexin 10 promotes triple-negative breast cancer progression through modulating cholesterol biosynthesis via stabilizing SREBP2.}},
author = {Yinping Guo and Jiahui Li and Wenjie Zhang and Min Xia and Gaohua Liu and Xiaolin Zhong and Yan Yi and Yajun Chen and Jing Zhong},
journal = {Cancer biology \& therapy},
year = {2026},
month = oct,
doi = {10.1080/15384047.2026.2749334},
url = {https://europepmc.org/article/MED/42895897},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Sorting nexin 10 promotes triple-negative breast cancer progression through modulating cholesterol biosynthesis via stabilizing SREBP2.
AU - Yinping Guo
AU - Jiahui Li
AU - Wenjie Zhang
AU - Min Xia
AU - Gaohua Liu
AU - Xiaolin Zhong
AU - Yan Yi
AU - Yajun Chen
AU - Jing Zhong
PY - 2026
DA - 2026/10/19
JO - Cancer biology & therapy
DO - 10.1080/15384047.2026.2749334
UR - https://europepmc.org/article/MED/42895897
AB - Objective Triple-negative breast cancer (TNBC) lacks effective therapeutics in clinical practice. Sorting nexin 10 (SNX10) plays essential roles in various cancers, and the role of SNX10 in TNBC remains unknown. This study investigated the role and action mechanism of SNX10 in TNBC.Methods Using the Kaplan-Meier Plotter database and bc-GenExMiner database to analyze the SNX10 expression and clinical significance. Functional assays, including MTT, colony formation, transwell assays, and xenograft experiments, were used to evaluate the role of SNX10 in TNBC. The GeneChip PrimeView Human Gene Expression Array was used to determine the downstream targets and pathways. Cholesterol levels and the expression of enriched cholesterol synthesis genes were detected by Filipin assay, RT-PCR, and Western Blot. The relationship of SNX10 and cholesterol biosynthesis was confirmed using CO-IP and immunofluorescence staining assays.Results SNX10 is positively related to poor prognosis of breast cancer and markedly up-regulated in TNBC. Knockdown of SNX10 suppressed cell proliferation, migration, and invasion, and slowed the tumor growth in vivo. Mechanistically, SNX10 positively regulates the content and distribution of cellular cholesterol, as does the expression of enriched cholesterol synthesis genes, and SNX10 interacts with SREBP2 and prolongs its half-life. Blocking with lovastatin, cholesterol, or siSREBP2 reversed these effects caused by altering SNX10 in TNBC cells in vitro.Conclusion SNX10 promoted TNBC progression through the regulation of cholesterol biosynthesis, which was mediated by interaction with SREBP2 and maintenance of its stability. SNX10 may be an effective therapeutic target for TNBC, and our study provides new insights into therapeutic strategies.
SN - 1538-4047
SN - 1555-8576
ER -