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

Jennifer C Coleman; Luke Tattersall; Val Yianni; Laura Knight; Hongqiang Yu; Sadie R Hallett; Philip Johnson; Ana J Caetano; Charlie Cosstick; Anne J Ridley; Alison Gartland; Maria R Conte; Agamemnon E Grigoriadis

doi:10.1016/j.isci.2024.109288

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

iScience. 2024 Feb 24;27(4):109288. doi: 10.1016/j.isci.2024.109288. eCollection 2024 Apr 19.

Authors

Affiliations

¹ Centre for Craniofacial & Regenerative Biology, King's College London, London, SE1 9RT UK.
² Randall Centre for Cell and Molecular Biophysics, King's College London, London, SE1 1UL UK.
³ The Mellanby Centre for Musculoskeletal Research, Department of Oncology and Metabolism, The University of Sheffield, Sheffield, S10 2RX UK.
⁴ School of Cellular and Molecular Medicine, University of Bristol, Bristol, BS8 1TD UK.

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.

Keywords: Biochemistry; Biological sciences; Cancer systems biology; Cell biology; Natural sciences; Systems biology.