Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages. Academic Article uri icon

Overview

abstract

  • Immunosuppressive tumor microenvironment (TME) and ascites-derived spheroids in ovarian cancer (OC) facilitate tumor growth and progression, and also pose major obstacles for cancer therapy. The molecular pathways involved in the OC-TME interactions, how the crosstalk impinges on OC aggression and chemoresistance are not well-characterized. Here, we demonstrate that tumor-derived UBR5, an E3 ligase overexpressed in human OC associated with poor prognosis, is essential for OC progression principally by promoting tumor-associated macrophage recruitment and activation via key chemokines and cytokines. UBR5 is also required to sustain cell-intrinsic β-catenin-mediated signaling to promote cellular adhesion/colonization and organoid formation by controlling the p53 protein level. OC-specific targeting of UBR5 strongly augments the survival benefit of conventional chemotherapy and immunotherapies. This work provides mechanistic insights into the novel oncogene-like functions of UBR5 in regulating the OC-TME crosstalk and suggests that UBR5 is a potential therapeutic target in OC treatment for modulating the TME and cancer stemness.

publication date

  • December 8, 2020

Research

keywords

  • Carcinoma, Ovarian Epithelial
  • Macrophages, Peritoneal
  • Ovarian Neoplasms
  • Peritoneal Neoplasms
  • Tumor Escape
  • Ubiquitin-Protein Ligases

Identity

PubMed Central ID

  • PMC7722725

Scopus Document Identifier

  • 85097444542

Digital Object Identifier (DOI)

  • 10.1016/j.jconrel.2014.04.057

PubMed ID

  • 33293516

Additional Document Info

volume

  • 11

issue

  • 1