ArticleOncotarget2014
CXCL12/CXCR4 signaling counteracts docetaxel-induced microtubule stabilization via p21-activated kinase 4-dependent activation of LIM domain kinase 1.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
47 citing papers in PubMed, 64 citations in OpenAlex.
- Phosphoproteomic Profiling Identifies PAK4 S474 Phosphorylation Affects Docetaxel Chemosensitivity via Modulation of Microtubule Stabilization in Breast Cancer.Biomedicines · 2026Article
- The interplay between p21-activated kinases and tumour-infiltrating dendritic cells and T cells and its implication in pancreatic cancer immunotherapy.Cell communication and signaling : CCS · 2026Review
- Prostate Cancer-Associated Fibroblasts: A Review on CAF Functions, Heterogeneity, Resistance Mechanisms, and Future in a Chip.International journal of molecular sciences · 2026Review
- Review
- Preparation, Optimization, and In-Vitro Evaluation of Brusatol- and Docetaxel-Loaded Nanoparticles for the Treatment of Prostate Cancer.Pharmaceutics · 2024Article
- Article
- Exploring the diversity of cancer-associated fibroblasts: insights into mechanisms of drug resistance.Frontiers in cell and developmental biology · 2024Review
- Review
- A CXCR4 inhibitor (balixafortide) enhances docetaxel-mediated antitumor activity in a murine model of prostate cancer bone metastasis.The Prostate · 2023Article
- Development and Characterization of Type I, Type II, and Type III LIM-Kinase Chemical Probes.Journal of medicinal chemistry · 2022Article
- Review
- MYB interacts with androgen receptor, sustains its ligand-independent activation and promotes castration resistance in prostate cancer.British journal of cancer · 2022Article
- Review
- The microtubule cytoskeleton: An old validated target for novel therapeutic drugs.Frontiers in pharmacology · 2022Review
- Article
- Article
- Article
- Acetylation of KLF5 maintains EMT and tumorigenicity to cause chemoresistant bone metastasis in prostate cancer.Nature communications · 2021Article
- Post-Translational Modifications That Drive Prostate Cancer Progression.Biomolecules · 2021Review
- Pyr1-Mediated Pharmacological Inhibition of LIM Kinase Restores Synaptic Plasticity and Normal Behavior in a Mouse Model of Schizophrenia.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Emerging data highlight the significance of chemokine (C-X-C motif) ligand 12/chemokine (C-X-C motif) receptor 4 (CXCL12/CXCR4) signaling axis in the chemoresistance of several malignancies, including prostate cancer (PCa); however, underlying mechanisms remain largely elusive. Here, we demonstrate that CXCL12 treatment rescues the PCa cells from docetaxel (DTX)-induced toxicity by overriding its effect on cell cycle (G2/M phase arrest). We further demonstrate that the chemoprotective effect of CXCL12 is abolished upon pharmacological inhibition or RNA interference-mediated silencing of CXCR4. Moreover, microtubule stabilization caused by DTX is suppressed in CXCL12-stimulated PCa cells as revealed by immunofluorescence and immunoblot analyses. The effect of CXCL12 on microtubule stabilization is abrogated when PCa cells are pre-treated with a CXCR4 antagonist. In additional studies, we show that the chemoprotective action of CXCL12/CXCR4 signaling is mediated by p21-activated kinase 4 (PAK4)-dependent activation of Lim domain kinase 1 (LIMK1), and inhibition of either PAK4 or LIMK1 leads to re-sensitization of PCa cells to DTX-induced tubulin polymerization and cellular toxicity even in the presence of CXCL12. Altogether, our findings uncover a novel mechanism underlying CXCL12/CXCR4 signaling-induced PCa chemoresistance and suggest that targeting of this signaling axis or its downstream effector pathway could lead to therapeutic enhancement of DTX.
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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.