4.5 Article

Neutrophil extracellular DNA traps promote pancreatic cancer cells migration and invasion by activating EGFR/ERK pathway

Journal

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 25, Issue 12, Pages 5443-5456

Publisher

WILEY
DOI: 10.1111/jcmm.16555

Keywords

EMT; IL‐ 1β NETs; Pancreatic Cancer

Funding

  1. National Natural Science Foundation of China [81601985, 81802380]

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NETs play important roles in the progression of pancreatic cancer, promoting migration, invasion, and epithelial-mesenchymal transition of cancer cells through the IL-1 beta/EGFR/ERK pathway. Targeting NETs may provide promising therapeutic strategies for pancreatic cancer.
Neutrophil extracellular DNA traps (NETs) are newly discovered forms of activated neutrophils. Increasing researches have shown that NETs play important roles in cancer progression. Our previous study has proved that tumour-infiltrating NETs could predict postsurgical survival in patients with pancreatic ductal adenocarcinoma (PDAC). However, the roles of NETs on the progression of pancreatic cancer are unknown. Here, we investigated the effects of NETs on pancreatic cancer cells. Results showed that both PDAC patients' and normal individuals' neutrophils-derived NETs could promote migration and invasion of pancreatic cancer cells with epithelial-mesenchymal transition. Further, study confirmed that EGFR/ERK pathway played an important role in this progression. The addition of neutralizing antibodies for IL-1 beta could effectively block the activation of EGFR/ERK companied with reduction of EMT, migration and invasion. Taken together, NETs facilitated EMT, migration and invasion via IL-1 beta/EGFR/ERK pathway in pancreatic cancer cells. Our study suggests that NETs may provide promising therapeutic targets for pancreatic cancer.

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