ArticleBreast cancer research : BCR2019
Rack1 mediates tyrosine phosphorylation of Anxa2 by Src and promotes invasion and metastasis in drug-resistant breast cancer cells.
Article in Breast cancer research : BCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 66 citations in OpenAlex.
- SMYD3 synergises with RACK1 to promote colorectal cancer lung metastasis by recruiting SMAD3.Cell communication and signaling : CCS · 2026Article
- HSPB1/KDM1 A facilitates ANXA2 expression via hypomethylated DNA promoter to inhibit ferroptosis and enhance gemcitabine resistance in pancreatic cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- ARID5A orchestrates cardiac aging and inflammation through MAVS mRNA stabilization.Nature cardiovascular research · 2025Article
- Engineering aptamer-directed phosphatase recruiting chimeras: a strategy for modulating receptor function and overcoming drug resistance.Nature communications · 2025Article
- ANXA2 in cancer: aberrant regulation of tumour cell apoptosis and its immune interactions.Cell death discovery · 2025Review
- Annexin A2: the feasibility of being a therapeutic target associated with cancer metastasis and drug resistance in cancer microenvironment.Discover oncology · 2024Review
- PIN1 promotes the metastasis of cholangiocarcinoma cells by RACK1-mediated phosphorylation of ANXA2.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- FAXC interacts with ANXA2 and SRC in mitochondria and promotes tumorigenesis in cholangiocarcinoma.Cancer science · 2024Article
- Annexin A2 combined with TTK accelerates esophageal cancer progression via the Akt/mTOR signaling pathway.Cell death & disease · 2024Article
- Article
- RACK1 Promotes Meningioma Progression by Activation of NF-κB Pathway via Preventing CSNK2B from Ubiquitination Degradation.Cancers · 2024Article
- RACK1 promotes the occurrence and progression of cervical carcinoma.Journal of clinical laboratory analysis · 2024Article
- METTL18 functions as a Phenotypic Regulator in Src-Dependent Oncogenic Responses of HER2-Negative Breast Cancer.International journal of biological sciences · 2024Article
- Lysyl oxidase-like 4 promotes the invasiveness of triple-negative breast cancer cells by orchestrating the invasive machinery formed by annexin A2 and S100A11 on the cell surface.Frontiers in oncology · 2024Article
- Role of c-Src in Carcinogenesis and Drug Resistance.Cancers · 2023Review
- RACK1 facilitates breast cancer progression by competitively inhibiting the binding of β-catenin to PSMD2 and enhancing the stability of β-catenin.Cell death & disease · 2023Article
- Analysis of differential membrane proteins related to matrix stiffness-mediated metformin resistance in hepatocellular carcinoma cells.Proteome science · 2023Article
- Collagen-I influences the post-translational regulation, binding partners and role of Annexin A2 in breast cancer progression.Frontiers in oncology · 2023Article
- The flavagline FL3 interferes with the association of Annexin A2 with the eIF4F initiation complex and transiently stimulates the translation ofFrontiers in cell and developmental biology · 2023Article
- FOXD1-dependent RalA-ANXA2-Src complex promotes CTC formation in breast cancer.Journal of experimental & clinical cancer research : CR · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAcquirement of resistance is always associated with a highly aggressive phenotype of tumor cells. Recent studies have revealed that Annexin A2 (Anxa2) is a key protein that links drug resistance and cancer metastasis. A high level of Anxa2 in cancer tissues is correlated to a highly aggressive phenotype. Increased Anxa2 expression appears to be specific in many drug-resistant cancer cells. The functional activity of Anxa2 is regulated by tyrosine phosphorylation at the Tyr23 site. Nevertheless, the accurate molecular mechanisms underlying the regulation of Anxa2 tyrosine phosphorylation and whether phosphorylation is necessary for the enhanced invasive phenotype of drug-resistant cells remain unknown.
methodsSmall interfering RNAs, small molecule inhibitors, overexpression, loss of function or gain of function, rescue experiments, Western blot, wound healing assays, transwell assays, and in vivo metastasis mice models were used to investigate the functional effects of Rack1 and Src on the tyrosine phosphorylation of Anxa2 and the invasion and metastatic potential of drug-resistant breast cancer cells. The interaction among Rack1, Src, and Anxa2 in drug-resistant cells was verified by co-immunoprecipitation assay.
resultsWe demonstrated that Anxa2 Tyr23 phosphorylation is necessary for multidrug-resistant breast cancer invasion and metastasis. Rack1 is required for the invasive and metastatic potential of drug-resistant breast cancer cells through modulating Anxa2 phosphorylation. We provided evidence that Rack1 acts as a signal hub and mediates the interaction between Src and Anxa2, thereby facilitating Anxa2 phosphorylation by Src kinase.
conclusionsOur findings suggest a convergence point role of Rack1/Src/Anxa2 complex in the crosstalk between drug resistance and cancer aggressiveness. The interaction between Anxa2 and Rack1/Src is responsible for the association between drug resistance and invasive/metastatic potential in breast cancer cells. Thus, our findings provide novel insights on the mechanism underlying the functional linkage between drug resistance and cancer aggressiveness.
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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.