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

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

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Article number109288
JournaliScience
Volume27
Issue number4
DOIs
Publication statusPublished - 19 Apr 2024

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