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Updated: Jan 31, 2026

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
ATG9A Is Overexpressed in Triple Negative Breast Cancer and Its In Vitro Extinction Leads to the Inhibition of
Aurore Claude-Taupin1, Leïla Fonderflick2, Thierry Gauthier3
1INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, University Bourgogne Franche-Comté F-25000 Besançon, France. taupin.aurore@gmail.com.
Abstract:
Early detection and targeted treatments have led to a significant decrease in mortality linked to breast cancer (BC), however, important issues need to be addressed in the future. One of them will be to find new triple negative breast cancer (TNBC) therapeutic strategies, since none are currently efficiently targeting this subtype of BC. Since numerous studies have reported the possibility of targeting the autophagy pathway to treat or limit cancer progression, we analyzed the expression of six autophagy genes (ATG9A, ATG9B, BECLIN1, LC3B, NIX and P62/SQSTM1) in breast cancer tissue, and compared their expression with healthy adjacent tissue. In our study, we observed an increase in ATG9A mRNA expression in TNBC samples from our breast cancer cohort. We also showed that this increase of the transcript was confirmed at the protein level on paraffin-embedded tissues. To corroborate these in vivo data, we designed shRNA- and CRISPR/Cas9-driven inhibition of ATG9A expression in the triple negative breast cancer cell line MDA-MB-436, in order to determine its role in the regulation of cancer phenotypes. We found that ATG9A inhibition led to an inhibition of in vitro cancer features, suggesting that ATG9A can be considered as a new marker of TNBC and might be considered in the future as a target to develop new specific TNBC therapies.
Insights
Triple negative breast cancer (TNBC) lacks targeted therapies. This study identifies ATG9A as upregulated in TNBC and demonstrates its inhibition reduces cancer cell features, suggesting ATG9A as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Breast cancer (BC) mortality has decreased due to early detection and targeted treatments.
- Triple negative breast cancer (TNBC) remains a challenge, lacking efficient targeted therapies.
- The autophagy pathway is being explored for cancer treatment strategies.
Purpose of the Study:
- To investigate the role of autophagy genes in breast cancer, particularly TNBC.
- To identify potential new therapeutic targets for TNBC.
- To analyze the expression of six autophagy genes in breast cancer tissues.
Main Methods:
- Compared expression of six autophagy genes (ATG9A, ATG9B, BECLIN1, LC3B, NIX, P62/SQSTM1) in breast cancer and adjacent healthy tissues.
- Validated ATG9A mRNA expression increase at the protein level in paraffin-embedded tissues.
- Utilized shRNA and CRISPR/Cas9 to inhibit ATG9A expression in MDA-MB-436 TNBC cell line.
Main Results:
- Observed increased ATG9A mRNA expression in TNBC samples.
- Confirmed elevated ATG9A protein levels in TNBC tissues.
- Demonstrated that ATG9A inhibition reduced in vitro cancer cell features.
Conclusions:
- ATG9A is upregulated in triple negative breast cancer.
- ATG9A plays a role in regulating cancer phenotypes.
- ATG9A represents a potential novel biomarker and therapeutic target for TNBC.
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