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Aldh1a3 accelerates lung metastasis of PDAC via enhancing tumor cells - lung epithelial cells cross talk through Sema4d-Plxnb1 and Sema3a-Nrp1 signaling

GSE248375 Mus musculus Expression profiling by high throughput sequencing 9 samples Submitted 2026/03/02 Platform GPL23479
Summary
In previous studies, we found that high expression of aldehyde dehydrogenase 1 family member A3 (ALDH1A3) was associated with more lymph node metastases in pancreatic ductal adenocarcinoma (PDAC). We here report in PDAC Aldh1a3 promotes lung colonization, while is dispensable in liver colonization or proliferation. Aldh1a3 upregulates the transcription of Plxnb1 and Nrp1 via accelerating acetylation at histone H3 lysine in the promoter regions of Plxnb1 and Nrp1. The enhancing signaling of Sema4d-Plxnb1 and Sema3a-Nrp1 between pancreatic cancer cells and lung epithelial cells facilitate tumor cells to colonize in the lung. Our studies have uncovered Aldh1a3 as a key regulator of semaphorin signaling. Sema4d-Plxnb1 and Sema3a-Nrp1 signaling is important for lung metastatic organotropism of PDAC, but is dispensable in liver metastasis.
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Also filed as BioProject PRJNA1043623 and SRA study SRP473261. Searching any of these in the dataset finder brings you back here.

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