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Notch signaling suppresses neuroendocrine differentiation and alters the tumor immune microenvironment in advanced prostate cancer

GSE234819 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2024/08/28 Platform GPL20301
Summary
Neuroendocrine prostate cancer (NEPC) is an aggressive, androgen-independent variant of prostate cancer (PCa) that most commonly develops in patients as a mechanism of therapeutic resistance. The underlying mechanisms driving PCa lineage plasticity and trans-differentiation to a neuroendocrine lineage are not fully understood. Here, we identify Notch signaling as a key suppressor of neuroendocrine differentiation in PCa. Restoration of Notch signaling in NEPC models results in phenotypic conversion towards a non-neuroendocrine state with expression of prostate luminal cell markers and immunologic changes including up-regulation of MHC Class I and II and type I interferon signaling that correlate with changes in the tumor immune microenvironment. Overall, these data provide new insights into how Notch signaling influences PCa lineage plasticity and points to new therapeutic avenues to modulate it.
Published in
Epigenetic Derepression of PROX1 Promotes Neuroendocrine Prostate Cancer Progression
Venkadakrishnan VB, Presser A, Voss NCE et al. · Cancer research 2025 · PMID 40838977 · doi:10.1158/0008-5472.CAN-25-0636
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Also filed as BioProject PRJNA983287 and SRA study SRP443240. Searching any of these in the dataset finder brings you back here.

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