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Cited by 15RNA Research and SplicingCancer-related Molecular PathwaysSarcoma Diagnosis and Treatment

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The RNA binding proteins LARP4A and LARP4B promote sarcoma and carcinoma growth and metastasis

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Coleman, Jennifer C., Tattersall, Luke, Yianni, Val, Knight, Laura, Yu, Hongqiang, Hallett, Sadie R., Johnson, Philip, Caetano, Ana J., Cosstick, Charlie, Ridley, Anne J., Gartland, Alison, Conte, Maria R., Grigoriadis, Agamemnon E.·2024·iScience
DOI 10.1016/j.isci.2024.109288PMC PMC10963253

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Abstract

RNA-binding proteins (RBPs) are emerging as important regulators of cancer pathogenesis. We reveal that the RBPs LARP4A and LARP4B are differentially overexpressed in osteosarcoma and osteosarcoma lung metastases, as well as in prostate cancer. Depletion of LARP4A and LARP4B reduced tumor growth and metastatic spread in xenografts, as well as inhibiting cell proliferation, motility, and migration. Transcriptomic profiling and high-content multiparametric analyses unveiled a central role for LARP4B, but not LARP4A, in regulating cell cycle progression in osteosarcoma and prostate cancer cells, potentially through modulating key cell cycle proteins such as Cyclins B1 and E2, Aurora B, and E2F1. This first systematic comparison between LARP4A and LARP4B assigns new pro-tumorigenic functions to LARP4A and LARP4B in bone and prostate cancer, highlighting their similarities while also indicating distinct functional differences. Uncovering clear biological roles for these paralogous proteins provides new avenues for identifying tissue-specific targets and potential druggable intervention.

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Metadata

Authors
Coleman, J. C., Tattersall, L., Yianni, V., Knight, L., Yu, H., Hallett, S. R., Johnson, P., Caetano, A. J., Cosstick, C., Ridley, A. J., Gartland, A., Conte, M. R., & Grigoriadis, A. E.
Affiliations
  • King's College London (GB)
  • University of Sheffield (GB)
  • University of Bristol (GB)
Corresponding author
  • Conte, Maria R.
  • Grigoriadis, Agamemnon E.
ORCID
Venue
iScience
Publisher
Elsevier BV
Published
2024-04
Volume
27
Issue
4
Pages
109288
ISSN
2589-0042 (ISSN-L)
DOI
10.1016/j.isci.2024.109288
PMC
PMC10963253
OpenAlex
W4392131697
Cited by
15
References
5
Citations by year
2026: 2 · 2025: 8 · 2024: 3
FWCI
1.77
Type
journal article
Language
en
Open access
Licence
Locations
  • iScience (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion, cc-by)
Funders
  • King's College London
  • Medical Research Council (MR/N013700/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
Keywords
LARP4B, RNA-binding proteins, osteosarcoma, prostate cancer, lung metastasis, tumor growth, cell cycle regulation, cyclin B1, cyclin E2, Aurora B kinase, E2F1, cell migration, cell proliferation, paralogous proteins

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