Notch signaling suppresses neuroendocrine differentiation and alters the immune microenvironment in advanced prostate cancer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39024561.
- Also identified by DOI 10.1172/JCI175217 and PMC identifier 11364388.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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).
Medical subject headings
- Prostatic Neoplasms
- Tumor Microenvironment
- Signal Transduction
- Cell Differentiation