ArticleOncotarget2016
ATG9A loss confers resistance to trastuzumab via c-Cbl mediated Her2 degradation.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Loss of Flotillin-2 enhances trastuzumab emtansine internalization and cytotoxicity by relieving negative regulation of HER2 internalization in HER2-amplified cancers.bioRxiv : the preprint server for biology · 2026Article
- Progress on multifunctional transmembrane protein ATG9A.Cell communication and signaling : CCS · 2025Review
- Targeting autophagy for breast cancer prevention and therapy: From classical methods to phytochemical agents.Iranian journal of basic medical sciences · 2024Review
- To eat or not to eat: a critical review on the role of autophagy in prostate carcinogenesis and prostate cancer therapeutics.Frontiers in pharmacology · 2024Review
- Role of K63-linked ubiquitination in cancer.Cell death discovery · 2022Review
- E3 Ubiquitin Ligase in Anticancer Drugdsla Resistance: Recent Advances and Future Potential.Frontiers in pharmacology · 2021Review
- Genome-Wide CRISPR Screen Reveals Autophagy Disruption as the Convergence Mechanism That Regulates the NRF2 Transcription Factor.Molecular and cellular biology · 2019Article
- Article
- Estradiol promotes rapid degradation of HER3 in ER-positive breast cancer cell line MCF-7.Biochemistry and biophysics reports · 2018Article
- Cleavage of the extracellular domain of junctional adhesion molecule-A is associated with resistance to anti-HER2 therapies in breast cancer settings.Breast cancer research : BCR · 2018Article
- Notch-1-PTEN-ERK1/2 signaling axis promotes HER2+ breast cancer cell proliferation and stem cell survival.Oncogene · 2018Article
- LMTK3 confers chemo-resistance in breast cancer.Oncogene · 2018Article
- Increased autophagy blocks HER2-mediated breast tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Deregulation of ATG9A by impaired AR signaling induces autophagy in prostate stromal fibroblasts and promotes BPH progression.Cell death & disease · 2018Article
- Interplay of autophagy, receptor tyrosine kinase signalling and endocytic trafficking.Essays in biochemistry · 2017Review
- Review
- BRAF, KRAS and PIK3CA Mutation and Sensitivity to Trastuzumab in Breast Cancer Cell Line ModelAsian Pacific journal of cancer prevention : APJCP · 2017Article
- Protein lysine methyltransferase SMYD3 is involved in tumorigenesis through regulation of HER2 homodimerization.Cancer medicine · 2017Article
- EGFR Family Members' Regulation of Autophagy Is at a Crossroads of Cell Survival and Death in Cancer.Cancers · 2017Review
- JWA down-regulates HER2 expression via c-Cbl and induces lapatinib resistance in human gastric cancer cells.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Acquired or de novo resistance to trastuzumab remains a barrier to patient survival and mechanisms underlying this still remain unclear. Using stable isotope labelling by amino acids in cell culture (SILAC)-based quantitative proteomics to compare proteome profiles between trastuzumab sensitive/resistant cells, we identified autophagy related protein 9A (ATG9A) as a down-regulated protein in trastuzumab resistant cells (BT474-TR). Interestingly, ATG9A ectopic expression markedly decreased the proliferative ability of BT474-TR cells but not that of the parental line (BT474). This was accompanied by a reduction of Her2 protein levels and AKT phosphorylation (S473), as well as a decrease in Her2 stability, which was also observed in JIMT1 and MDA-453, naturally trastuzumab-resistant cells. In addition, ATG9A indirectly promoted c-Cbl recruitment to Her2 on T1112, a known c-Cbl docking site, leading to increased K63 Her2 polyubiquitination. Whereas silencing c-Cbl abrogated ATG9A repressive effects on Her2 and downstream PI3K/AKT signaling, its depletion restored BT474-TR proliferative rate. Taken together, our findings show for this first time that ATG9A loss in trastuzumab resistant cells allowed Her2 to escape from lysosomal targeted degradation through K63 poly-ubiquitination via c-Cbl. This study identifies ATG9A as a potentially druggable target to overcome resistance to anti-Her2 blockade.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.