2. Academic Validation
  3. Necroptosis enhances 'don't eat me' signal and induces macrophage extracellular traps to promote pancreatic cancer liver metastasis

Necroptosis enhances 'don't eat me' signal and induces macrophage extracellular traps to promote pancreatic cancer liver metastasis

  • Nat Commun. 2024 Jul 18;15(1):6043. doi: 10.1038/s41467-024-50450-6.
Cheng-Yu Liao # 1 2 3,  Ge Li # 4,  Feng-Ping Kang # 1,  Cai-Feng Lin 1 2 3,  Cheng-Ke Xie 1 2,  Yong-Ding Wu 1 2,  Jian-Fei Hu 1 2,  Hong-Yi Lin 1 2,  Shun-Cang Zhu 1 2,  Xiao-Xiao Huang 1 2 3,  Jian-Lin Lai 1 2 3,  Li-Qun Chen 3,  Yi Huang 1 3,  Qiao-Wei Li 1 5 6,  Long Huang 1 2 3,  Zu-Wei Wang 7 8 9,  Yi-Feng Tian 10 11 12,  Shi Chen 13 14 15 16 17
Affiliations

Affiliations

  • 1 Shengli Clinical Medical College of Fujian Medical University, 350001, Fuzhou, China.
  • 2 Department of Hepatobiliary Pancreatic Surgery, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, 350001, Fuzhou, China.
  • 3 Fuzhou University, 350001, Fuzhou, China.
  • 4 Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, 350001, Fuzhou, China.
  • 5 Fujian Provincial Center for Geriatrics, 350001, Fuzhou, China.
  • 6 Fujian Key Laboratory of Geriatrics, 350001, Fuzhou, China.
  • 7 Shengli Clinical Medical College of Fujian Medical University, 350001, Fuzhou, China. drzuwei123@163.com.
  • 8 Department of Hepatobiliary Pancreatic Surgery, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, 350001, Fuzhou, China. drzuwei123@163.com.
  • 9 Fuzhou University, 350001, Fuzhou, China. drzuwei123@163.com.
  • 10 Shengli Clinical Medical College of Fujian Medical University, 350001, Fuzhou, China. tianyifeng@fjmu.edu.cn.
  • 11 Department of Hepatobiliary Pancreatic Surgery, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, 350001, Fuzhou, China. tianyifeng@fjmu.edu.cn.
  • 12 Fuzhou University, 350001, Fuzhou, China. tianyifeng@fjmu.edu.cn.
  • 13 Shengli Clinical Medical College of Fujian Medical University, 350001, Fuzhou, China. wawljwalj@163.com.
  • 14 Department of Hepatobiliary Pancreatic Surgery, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, 350001, Fuzhou, China. wawljwalj@163.com.
  • 15 Fuzhou University, 350001, Fuzhou, China. wawljwalj@163.com.
  • 16 Fujian Provincial Center for Geriatrics, 350001, Fuzhou, China. wawljwalj@163.com.
  • 17 Fujian Key Laboratory of Geriatrics, 350001, Fuzhou, China. wawljwalj@163.com.
  • # Contributed equally.
PMID: 39025845 DOI: 10.1038/s41467-024-50450-6
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a devastating Cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA Sequencing and multiplex immunofluorescence, here we find elevated expression of Mixed Lineage Kinase domain-like pseudo-kinase (MLKL) and enhanced Necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven Necroptosis recruits macrophages, enhances the tumor CD47 'don't eat me' signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial-mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting Necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that Necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z