ArticleThe Journal of biological chemistry2010
RHAMM promotes interphase microtubule instability and mitotic spindle integrity through MEK1/ERK1/2 activity.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 98 citations in OpenAlex.
- Stress adaptation pathways and HA-CD44 signaling maintain the survival of pancreatic cancer cells with centrosome amplification.Cell communication and signaling : CCS · 2026Article
- Hyaluronan induces ERK activation with minimal transcriptomic changes in pancreatic α-cells.Biochemistry and biophysics reports · 2026Article
- Node properties of biomarkers within the protein-protein interaction network derived from breast cancer-associated genes.PloS one · 2026Article
- HMMR in human cancers: regulatory mechanism and biological function.Journal of translational medicine · 2025Review
- Article
- Targeting RHAMM in Cancer: Crosstalk with Non-Coding RNAs and Emerging Therapeutic Strategies Including Peptides, Oligomers, Antibodies, and Vaccines.International journal of molecular sciences · 2025Review
- Modulation of the cytoskeleton for cancer therapy.Frontiers in cell and developmental biology · 2025Article
- The truncated isoform of the receptor for hyaluronan-mediated motility (RHAMMFrontiers in aging · 2025Article
- Microtubule regulation in cancer cells.Frontiers in cell and developmental biology · 2025Article
- Biomimetic Hyaluronan Binding Biomaterials to Capture the Complex Regulation of Hyaluronan in Tissue Development and Function.Biomimetics (Basel, Switzerland) · 2024Review
- Article
- Exploring HMMR as a therapeutic frontier in breast cancer treatment, its interaction with various cell cycle genes, and targeting its overexpression through specific inhibitors.Frontiers in pharmacology · 2024Article
- Targeting hyaluronan-mediated motility receptor (HMMR) enhances response to androgen receptor signalling inhibitors in prostate cancer.British journal of cancer · 2023Article
- Glioma Stem Cells Are Sensitized to BCL-2 Family Inhibition by Compromising Histone Deacetylases.International journal of molecular sciences · 2023Article
- Hyaluronan and Reactive Oxygen Species Signaling-Novel Cues from the Matrix?Antioxidants (Basel, Switzerland) · 2023Review
- Hyaluronan Receptors as Mediators and Modulators of the Tumor Microenvironment.Advanced healthcare materials · 2023Review
- Hyaluronan breakdown by snake venom hyaluronidases: From toxins delivery to immunopathology.Frontiers in immunology · 2023Review
- "Annals of pancreatic cancer · 2022Article
- Hyaluronic Acid: Known for Almost a Century, but Still in Vogue.Pharmaceutics · 2022Review
- Screening a novel six critical gene-based system of diagnostic and prognostic biomarkers in prostate adenocarcinoma patients with different clinical variables.American journal of translational research · 2022Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
An oncogenic form of RHAMM (receptor for hyaluronan-mediated motility, mouse, amino acids 163-794 termed RHAMM(Delta163)) is a cell surface hyaluronan receptor and mitotic spindle protein that is highly expressed in aggressive human cancers. Its regulation of mitotic spindle integrity is thought to contribute to tumor progression, but the molecular mechanisms underlying this function have not previously been defined. Here, we report that intracellular RHAMM(Delta163) modifies the stability of interphase and mitotic spindle microtubules through ERK1/2 activity. RHAMM(-/-) mouse embryonic fibroblasts exhibit strongly acetylated interphase microtubules, multi-pole mitotic spindles, aberrant chromosome segregation, and inappropriate cytokinesis during mitosis. These defects are rescued by either expression of RHAMM or mutant active MEK1. Mutational analyses show that RHAMM(Delta163) binds to alpha- and beta-tubulin protein via a carboxyl-terminal leucine zipper, but in vitro analyses indicate this interaction does not directly contribute to tubulin polymerization/stability. Co-immunoprecipitation and pulldown assays reveal complexes of RHAMM(Delta163), ERK1/2-MEK1, and alpha- and beta-tubulin and demonstrate direct binding of RHAMM(Delta163) to ERK1 via a D-site motif. In vitro kinase analyses, expression of mutant RHAMM(Delta163) defective in ERK1 binding in mouse embryonic fibroblasts, and blocking MEK1 activity collectively confirm that the effect of RHAMM(Delta163) on interphase and mitotic spindle microtubules is mediated by ERK1/2 activity. Our results suggest a model wherein intracellular RHAMM(Delta163) functions as an adaptor protein to control microtubule polymerization during interphase and mitosis as a result of localizing ERK1/2-MEK1 complexes to their tubulin-associated substrates.
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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.