ArticleCell reports. Medicine2022
PSMG2-controlled proteasome-autophagy balance mediates the tolerance for MEK-targeted therapy in triple-negative breast cancer.
Article in Cell reports. Medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Dihydroartemisinin inhibits mutant KRAS to potentiate regorafenib plus anti-PD-1 in KRAS-mutant colorectal cancer liver metastases.Cell death & disease · 2026Article
- Phenotyping of post-fertilization sperm mitophagy determinants discovered in a mammalian gamete-based cell-free system.Biological research · 2026Article
- H3K18la-PSMG1 Axis in Bladder Cancer Progression: Curcumin as a Therapeutic Candidate.International journal of biological sciences · 2026Article
- Data-independent acquisition quantitative proteomics analysis of milk fat globule membrane proteins in rabbit colostrum and mature milk.Frontiers in veterinary science · 2026Article
- Review
- Targeting LINC02320 prevents colorectal cancer growth via GRB7-dependent inhibition of MAPK signaling pathway.Cellular & molecular biology letters · 2025Article
- CRISPR screening approaches in breast cancer research.Cancer metastasis reviews · 2025Review
- CEACAM6 as a machine learning derived immune biomarker for predicting neoadjuvant chemotherapy response in HR+/HER2- breast cancer.Frontiers in immunology · 2025Article
- Recent Advances in Immunotherapy and Targeted Therapy of Triple Negative Breast Cancer.Current pharmaceutical biotechnology · 2025Review
- Article
- Ubiquitination regulates autophagy in cancer: simple modifications, promising targets.Journal of translational medicine · 2024Review
- Microglial CMPK2 promotes neuroinflammation and brain injury after ischemic stroke.Cell reports. Medicine · 2024Article
- Small molecule agents for triple negative breast cancer: Current status and future prospects.Translational oncology · 2024Review
- Applications of CRISPR Technology to Breast Cancer and Triple Negative Breast Cancer Research.Cancers · 2023Review
- Identifying CDC7 as a synergistic target of chemotherapy in resistant small-cell lung cancer via CRISPR/Cas9 screening.Cell death discovery · 2023Article
- AGR2: a secreted protein worthy of attention in diagnosis and treatment of breast cancer.Frontiers in oncology · 2023Review
- CRISPR/Cas9 as a therapeutic tool for triple negative breast cancer: from bench to clinics.Frontiers in molecular biosciences · 2023Review
- Immune-based combination therapy for esophageal cancer.Frontiers in immunology · 2022Review
- WXJ-202, a novel Ribociclib derivative, exerts antitumor effects against breast cancer through CDK4/6.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the MAPK pathway is aberrantly activated in triple-negative breast cancers (TNBCs), the clinical outcome of MEK-targeted therapy is still poor. Through a genome-wide CRISPR-Cas9 library screening, we find that inhibition of PSMG2 sensitizes TNBC cells BT549 and MB468 to the MEK inhibitor AZD6244. Mechanistically, PSMG2 knockdown impairs proteasome function, which in turn activates autophagy-mediated PDPK1 degradation. The PDPK1 degradation significantly enhances AZD6244-induced tumor cell growth inhibition by interrupting the negative feedback signals toward the AKT pathway. Consistently, co-targeting proteasomes and MEK with inhibitors synergistically suppresses tumor cell growth. The autophagy inhibitor chloroquine partially relieves the PDPK1 degradation and reverses the growth inhibition induced by combinatorial inhibition of MEK and proteasome. The combination regimen with the proteasome inhibitor MG132 plus AZD6244 synergistically inhibits tumor growth in a 4T1 xenograft mouse model. In summary, our study not only unravels the mechanism of MEK inhibitor resistance but also provides a combinatorial therapeutic strategy for TNBC in clinics.
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