Notch signaling suppresses neuroendocrine differentiation and alters the immune microenvironment in advanced prostate cancer. Academic Article uri icon

Overview

abstract

  • Notch signaling can have either an oncogenic or tumor-suppressive function in cancer depending on the cancer type and cellular context. While Notch can be oncogenic in early prostate cancer, we identified significant downregulation of the Notch pathway during prostate cancer progression from adenocarcinoma to neuroendocrine (NE) prostate cancer, where it functions as a tumor suppressor. Activation of Notch in NE and Rb1/Trp53-deficient prostate cancer models led to phenotypic conversion toward a more indolent, non-NE state with glandular features and expression of luminal lineage markers. This was accompanied by upregulation of MHC and type I IFN and immune cell infiltration. Overall, these data support Notch signaling as a suppressor of NE differentiation in advanced prostate cancer and provide insights into how Notch signaling influences lineage plasticity and the tumor microenvironment (TME).

publication date

  • July 18, 2024

Research

keywords

  • Cell Differentiation
  • Prostatic Neoplasms
  • Signal Transduction
  • Tumor Microenvironment

Identity

PubMed Central ID

  • PMC11364388

Scopus Document Identifier

  • 85203204459

Digital Object Identifier (DOI)

  • 10.1172/JCI175217

PubMed ID

  • 39024561

Additional Document Info

volume

  • 134

issue

  • 17