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Updated: Jan 13, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Artemis (DCLRE1C) Acts as a Target to Enhance Radiotherapy Response in Triple-Negative Breast Cancer
Vasudeva Bhat1,2,3, Kelsie L Thu4,5, Anayra de Fatima Goncalves Santiago1
1Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 3K7, Canada.
Background/Objectives:
The lack of canonical biomarkers and strategies to target radioresistance contribute to poor patient outcomes in triple-negative breast cancer (TNBC). Identifying and targeting novel radioresistance genes will benefit in enhancing radiotherapy response and treatment outcomes in TNBC patients.
Methods:
A genome-wide CRISPR screen was performed to identify radioresistance genes in the TNBC cell line. An in vitro clonogenic assay was used to assess the antiproliferative effects of Artemis knockout or pharmacologic inhibition of Artemis, either alone or in combination with RT. Tumor doubling time and animal survival were assessed using an in vivo xenograft model. RNA-seq analysis was performed to identify genes and pathways deregulated under Artemis knockout conditions, both alone and in combination with RT. Cellular senescence was evaluated using a β-galactosidase assay.
Results:
Our CRISPR screen identified Artemis as a top hit in RT-treated TNBC cells, whose depletion led to radiosensitization in TNBC. Artemis knockout significantly reduced cell proliferation and enhanced the antiproliferative effects of RT in vitro. Compared to mice-bearing control MDA-MB-231 xenografts, Artemis knockout exhibited prolonged survival that was further enhanced with RT. Bulk RNA-sequencing indicated that the antiproliferative and radiosensitization effects of Artemis depletion were mediated by the activation of cellular senescence which was confirmed with a β-galactosidase assay.
Conclusions:
Taken together, our results highlight the critical role of Artemis in TNBC cell proliferation and response to radiation. Our findings identify Artemis as a potential biomarker indicative of sensitivity to radiation and a putative target that could be inhibited to enhance the efficacy of RT in TNBC.
Insights
Targeting Artemis, a novel radioresistance gene, can enhance radiotherapy response in triple-negative breast cancer (TNBC). Inhibiting Artemis promotes radiosensitization and improves treatment outcomes for TNBC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Triple-negative breast cancer (TNBC) lacks biomarkers and effective strategies against radioresistance, leading to poor outcomes.
- Identifying novel radioresistance genes is crucial for improving radiotherapy response in TNBC.
Purpose of the Study:
- To identify and characterize novel radioresistance genes in TNBC.
- To evaluate Artemis as a potential therapeutic target to enhance radiotherapy efficacy in TNBC.
Main Methods:
- Genome-wide CRISPR screen in TNBC cells to identify radioresistance genes.
- In vitro and in vivo assays (clonogenic, xenograft) to assess Artemis function and radiosensitization.
- RNA-sequencing and senescence assays to elucidate underlying mechanisms.
Main Results:
- Artemis was identified as a key radioresistance gene in TNBC.
- Artemis knockout sensitized TNBC cells to radiation, reducing proliferation and enhancing RT effects in vitro and in vivo.
- Artemis depletion induced cellular senescence, mediating its radiosensitizing effects.
Conclusions:
- Artemis plays a critical role in TNBC proliferation and radioresistance.
- Artemis is a potential biomarker for radiation sensitivity and a therapeutic target to improve RT efficacy in TNBC.
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