ArticleBreast cancer research : BCR2013
A mammosphere formation RNAi screen reveals that ATG4A promotes a breast cancer stem-like phenotype.
Article in Breast cancer research : BCR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 132 citations in OpenAlex.
- Decoding triple negative breast cancer bone metastasis: from 3D bioprinted models to clinical translation.Journal of nanobiotechnology · 2026Review
- ABCG2-autophagy regulatory axis in cancer stem cells: implication in cancer metastasis, recurrence and chemotherapy resistance.Cell communication and signaling : CCS · 2026Review
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- Largazole targets Musashi protein expression via miR-125b-5p and sensitizes triple-negative breast cancer cells to radiation.Frontiers in pharmacology · 2026Article
- Unraveling autophagy-metabolism crosstalk in cancer: Molecular insights and therapeutic strategies.Theranostics · 2026Review
- Autophagy Protease ATG4D Facilitates Proliferation and Malignancy of Osteosarcoma Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- The dual role of autophagy in cancer stem cells: implications for tumor progression and therapy resistance.Journal of translational medicine · 2025Review
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- Autophagy in brain tumors: molecular mechanisms, challenges, and therapeutic opportunities.Journal of translational medicine · 2025Review
- The IPBiochimica et biophysica acta. Molecular basis of disease · 2025Article
- Autophagy as a Therapeutic Target in Breast Tumors: The Cancer stem cell perspective.Autophagy reports · 2024Article
- Autophagy and cancer therapy.Cancer letters · 2024Review
- Role of Autophagy and AMPK in Cancer Stem Cells: Therapeutic Opportunities and Obstacles in Cancer.International journal of molecular sciences · 2024Review
- Enhancing Therapeutic Efficacy in Cancer Treatment: Integrating Nanomedicine with Autophagy Inhibition Strategies.ACS omega · 2024Review
- Dissecting the multifaceted roles of autophagy in cancer initiation, growth, and metastasis: from molecular mechanisms to therapeutic applications.Medical oncology (Northwood, London, England) · 2024Review
- The multifaceted role of extracellular vesicles (EVs) in colorectal cancer: metastasis, immune suppression, therapy resistance, and autophagy crosstalk.Journal of translational medicine · 2024Review
- Spheroid architecture strongly enhances miR-221/222 expression and promotes oxidative phosphorylation in an ovarian cancer cell line through a mechanism that includes restriction of miR-9 expression.Molecular biology reports · 2024Article
- Protein tyrosine phosphatase PTPH1 potentiates receptor tyrosine kinase HER2 oncogenesis via a PDZ-coupled and phosphorylation-driven scaffold.American journal of cancer research · 2024Article
- Loss of ATG4B and ATG4A results in two-stage cell cycle defects in pancreatic ductal adenocarcinoma cells.Journal of cell science · 2023Article
- Impact of context-dependent autophagy states on tumor progression.Nature cancer · 2023Review
22 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
introductionBreast cancer stem cells are suspected to be responsible for tumour recurrence, metastasis formation as well as chemoresistance. Consequently, great efforts have been made to understand the molecular mechanisms underlying cancer stem cell maintenance. In order to study these rare cells in-vitro, they are typically enriched via mammosphere culture. Here we developed a mammosphere-based negative selection shRNAi screening system suitable to analyse the involvement of thousands of genes in the survival of cells with cancer stem cell properties.
methodsWe describe a sub-population expressing the stem-like marker CD44(+)/CD24(-/low) in SUM149 that were enriched in mammospheres. To identify genes functionally involved in the maintenance of the sub-population with cancer stem cell properties, we targeted over 5000 genes by RNAi and tested their ability to grow as mammospheres. The identified candidate ATG4A was validated in mammosphere and soft agar colony formation assays. Further, we evaluated the influence of ATG4A expression on the sub-population expressing the stem-like marker CD44(+)/CD24(low). Next, the tumorigenic potential of SUM149 after up- or down-regulation of ATG4A was examined by xenograft experiments.
resultsUsing this method, Jak-STAT as well as cytokine signalling were identified to be involved in mammosphere formation. Furthermore, the autophagy regulator ATG4A was found to be essential for the maintenance of a sub-population with cancer stem cell properties and to regulate breast cancer cell tumourigenicity in vivo.
conclusionIn summary, we present a high-throughput screening system to identify genes involved in cancer stem cell maintenance and demonstrate its utility by means of ATG4A.
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