Targeting ubiquitin protein ligase E3 component N-recognin 5 in cancer cells induces a CD8+ T cell mediated immune response. Academic Article uri icon

Overview

abstract

  • UBR5 is a nuclear phosphoprotein of obscure functions. Clinical analyses reveal that UBR5 amplifications and overexpression occur in over 20% cases of human breast cancers. Breast cancer patients carrying UBR5 genetic lesions with overexpression have significantly reduced survival. Experimental work in vitro and in vivo demonstrates that UBR5, functioning as an oncoprotein, plays a profound role in breast cancer growth and metastasis. UBR5 drives tumor growth largely through paracrine interactions with the immune system, particularly through inhibiting the cytotoxic response mediated by CD8+ T lymphocytes, whereas it facilitates metastasis in a tumor cell-autonomous manner via its transcriptional control of key regulators of the epithelial-mesenchymal transition, ID1 and ID3. Furthermore, simultaneous targeting of UBR5 and PD-L1 yields strong therapeutic benefit to tumor-bearing hosts. This work significantly expands our scarce understanding of the pathophysiology and immunobiology of a fundamentally important molecule and has strong implications for the development of novel immunotherapy to treat highly aggressive breast cancers that resist conventional treatment.

publication date

  • April 14, 2020

Research

keywords

  • Breast Neoplasms
  • Ubiquitin-Protein Ligases

Identity

PubMed Central ID

  • PMC7185213

Scopus Document Identifier

  • 85083560217

Digital Object Identifier (DOI)

  • 10.1016/j.bbamcr.2007.11.015

PubMed ID

  • 32363114

Additional Document Info

volume

  • 9

issue

  • 1