ArticleCell death & disease2019
Rack1 mediates Src binding to drug transporter P-glycoprotein and modulates its activity through regulating Caveolin-1 phosphorylation in breast cancer cells.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 52 citations in OpenAlex.
- Extracellular vesicles shed by multidrug resistant cells contribute to the identification of SRC inhibitors as chemosensitizers in non-small cell lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2026Article
- Roles of Post-Translational Modifications of Transcription Factors Involved in Breast Cancer Hypoxia.Molecules (Basel, Switzerland) · 2025Review
- From Psychiatry to Oncology: Exploring the Anti-Neoplastic Mechanisms of Aripiprazole and Its Potential Use in Cancer Treatment.Pharmacology research & perspectives · 2025Review
- Bio-Pathological Functions of Posttranslational Modifications of Histological Biomarkers in Breast Cancer.Molecules (Basel, Switzerland) · 2024Review
- Oligomerization of drug transporters: Forms, functions, and mechanisms.Acta pharmaceutica Sinica. B · 2024Review
- Role of c-Src in Carcinogenesis and Drug Resistance.Cancers · 2023Review
- Loss of SMURF2 expression enhances RACK1 stability and promotes ovarian cancer progression.Cell death and differentiation · 2023Article
- Estrogen-related genes for thyroid cancer prognosis, immune infiltration, staging, and drug sensitivity.BMC cancer · 2023Article
- 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
- Establishing protein expression profiles involved in tooth development using a proteomic approach.Odontology · 2023Article
- The c-Src/LIST Positive Feedback Loop Sustains Tumor Progression and Chemoresistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Article
- Caveolae-Associated Molecules, Tumor Stroma, and Cancer Drug Resistance: Current Findings and Future Perspectives.Cancers · 2022Review
- Graphene-based nanomaterials for breast cancer treatment: promising therapeutic strategies.Journal of nanobiotechnology · 2021Review
- Dissecting immune cell stat regulation network reveals biomarkers to predict ICB therapy responders in melanoma.Journal of translational medicine · 2021Article
- Molecular Regulation of Canalicular ABC Transporters.International journal of molecular sciences · 2021Review
- Mitochondrial Breast Cancer Resistant Protein Sustains the Proliferation and Survival of Drug-Resistant Breast Cancer Cells by Regulating Intracellular Reactive Oxygen Species.Frontiers in cell and developmental biology · 2021Article
- SHP2 promotes proliferation of breast cancer cells through regulating Cyclin D1 stabilityCancer biology & medicine · 2020Article
- pH and redox dual-responsive nanoparticles based on disulfide-containing poly(β-amino ester) for combining chemotherapy and COX-2 inhibitor to overcome drug resistance in breast cancer.Journal of nanobiotechnology · 2019Article
- Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The failure of chemotherapy and the emergence of multidrug resistance (MDR) are the major obstacles for effective therapy in locally advanced and metastatic breast cancer. Overexpression of the drug transporter P-glycoprotein (P-gp) in cancer cells is one of the main causes of MDR due to its ability to efflux anticancer drugs out of cells. Although the signaling node that regulates the expression of P-gp has been intensively investigated; the regulatory mechanism underlying P-gp transport activity remains obscure. Herein, we reported that Rack1 and tyrosine kinase Src confer drug resistance through modulating the transport function of P-gp without altering its protein level. We provide evidences that Rack1 and Src regulate P-gp activity by modulating caveolin-1 (Cav1) phosphorylation. Importantly, Rack1 acts as a signaling hub and mediates Src binding to P-gp, thereby facilitating the phosphorylation of Cav1 by Src and abolishing the inhibitory effect of Cav1 on P-gp. Taken together, our results demonstrate the pivotal roles of Rack1 and Src in modulating P-gp activity in drug-resistant cells. Our findings also provide novel insights into the mechanism regulating P-gp transport activity. Rack1 may represent a new target for the development of effective therapies for reversing drug resistance.
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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.