ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Steroid Receptor Coactivator-1 Drives Tumor-Associated Macrophage Reprogramming by Mediating MMP12 Transcription in Pancreatic Cancer Perineural Invasion.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Neural-immune-cancer crosstalk in pancreatic cancer: mechanisms and clinical translation.Frontiers in cell and developmental biology · 2026Review
- Steroid Receptor Coactivator-1 Drives Tumor-Associated Macrophage Reprogramming by Mediating MMP12 Transcription in Pancreatic Cancer Perineural Invasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Perineural invasion (PNI) is a hallmark of pancreatic cancer aggressiveness. However, the feasibility of manipulating tumor-associated macrophage (TAM) reprogramming to influence PNI development remains unclear. Methods: Using in vitro (tumor-DRG co-culture) and in vivo (sciatic nerve injection) models coupled with protein identification by liquid chromatography-mass spectrometry (LC-MS) and ChIP-seq, the role of steroid receptor coactivator-1 (SRC-1) is investigated in TAM reprogramming and PNI. SRC-1 is up-regulated in TAMs and promotes PNI by binding to signal transducer and activator of transcription 1(STAT1) to enhance matrix metallopeptidase 12 (MMP12) transcription. SRC-1 knockdown attenuated M2-like characteristics in TAMs, reduced MMP12 secretion, and suppressed PNI. Importantly, blocking the SRC-1/STAT1/MMP12 axis (using SRC-1-KO TAMs or MMP12 inhibitors) attenuated PNI progression in vivo. SRC-1 reprograms TAMs via STAT1-mediated MMP12 activation to facilitate PNI. Targeting SRC-1 disrupts this axis and presents a novel therapeutic strategy against PNI in pancreatic cancer.
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Registered trials
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