ArticleCell death & disease2021
Mutant p53 promotes RCP-dependent chemoresistance coinciding with increased delivery of P-glycoprotein to the plasma membrane.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Reactivation ofInternational journal of molecular sciences · 2026Article
- Δ133p53 isoform enhances TLR4 function to promote tumor growth.Carcinogenesis · 2025Article
- Chemotherapy enhances HMGA1 secretion through the mutant p53-CK2 axis in pancreatic ductal adenocarcinoma cells.Cell death & disease · 2025Article
- Mutant p53 induces SH3BGRL expression to promote cell engulfment.Cell death discovery · 2025Article
- Regulatory mechanism of ABCB1 transcriptional repression by HDAC5 in rat hepatocytes under hypoxic environment.Frontiers in physiology · 2025Article
- An Overview of Altered Pathways Associated with Sensitivity to Platinum-Based Chemotherapy in Neuroendocrine Tumors: Strengths and Prospects.International journal of molecular sciences · 2024Review
- Combined in vitro/in vivo genome-wide CRISPR screens in triple negative breast cancer identify cancer stemness regulators in paclitaxel resistance.Oncogenesis · 2023Article
- AGA induces sub-G1 cell cycle arrest and apoptosis in human colon cancer cells through p53-independent/p53-dependent pathway.BMC cancer · 2023Article
- p53 Modulates Radiosensitivity in Head and Neck Cancers-From Classic to Future Horizons.Diagnostics (Basel, Switzerland) · 2022Review
- GOF Mutant p53 in Cancers: A Therapeutic Challenge.Cancers · 2022Review
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- Activatable "Matryoshka" nanosystem delivery NgBR siRNA and control drug release for stepwise therapy and evaluate drug resistance cancer.Materials today. Bio · 2022Article
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- Activation ofCancers · 2022Article
- Review
- iRFP (near-infrared fluorescent protein) imaging of subcutaneous and deep tissue tumours in mice highlights differences between imaging platforms.Cancer cell international · 2021Article
- Rab11-FIP1/RCP Functions as a Major Signalling Hub in the Oncogenic Roles of Mutant p53 in Cancer.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
TP53 is the most frequently mutated gene in cancers. Mutations lead to loss of p53 expression or expression of a mutant protein. Mutant p53 proteins commonly lose wild-type function, but can also acquire novel functions in promoting metastasis and chemoresistance. Previously, we uncovered a role for Rab-coupling protein (RCP) in mutant p53-dependent invasion. RCP promotes endosomal recycling and signalling of integrins and receptor tyrosine kinases. In a screen to identify novel RCP-interacting proteins, we discovered P-glycoprotein (P-gp). Thus, we hypothesised that mutant p53 could promote chemoresistance through RCP-dependent recycling of P-gp. The interaction between RCP and P-gp was verified endogenously and loss of RCP or mutant p53 rendered cells more sensitive to cisplatin and etoposide. In mutant p53 cells we detected an RCP-dependent delivery of P-gp to the plasma membrane upon drug treatment and decreased retention of P-gp substrates. A co-localisation of P-gp and RCP was seen in mutant p53 cells, but not in p53-null cells upon chemotherapeutic exposure. In conclusion, mutant p53 expression enhanced co-localisation of P-gp and RCP to allow for rapid delivery of P-gp to the plasma membrane and increased resistance to chemotherapeutics.
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