LRG-1 promotes pancreatic cancer growth and metastasis via modulation of the EGFR/p38 signaling

J Exp Clin Cancer Res. 2019 Feb 13;38(1):75. doi: 10.1186/s13046-019-1088-0.


Background: The abnormal expression of leucine-rich-alpha-2-glycoprotein 1 (LRG-1) is reported to be associated with multiple malignancies, but its role in the progression of pancreatic ductal adenocarcinoma (PDAC) remains to be determined.

Methods: The expression of LRG-1 was assessed in PDAC tissues by RT-PCR, Western blot and immunohistochemistry. LRG-1-silenced or overexpressed cell lines were constructed using shRNA or LRG-1-overexpressing plasmids. EdU incorporation assay, Transwell invasion and wound-healing assays were performed to evaluate the proliferation, invasion and migration of PDAC cells. In addition, protein expression of the mitogen-activated protein kinase (MAPK) pathway was detected using Western blot. Finally, Co-immunoprecipitation assay was conducted in search of the potential interaction between LRG-1 and epidermal growth factor receptor (EGFR).

Results: The expression of LRG-1 in PDAC tissue was significantly higher than that in adjacent normal tissue, and high LRG-1 expression predicted poor survival and a late tumor stage. In addition, LRG-1 markedly promoted the viability, proliferation, migration and invasion of PDAC cells in vitro and facilitated tumor growth in vivo. More importantly, we revealed that these bioactivities of LRG-1 might result from its selective interaction with EGFR, which might further activate the p38/MAPK signaling pathways.

Conclusion: LRG-1 may prove to be a promising biomarker for predicting prognosis of PDAC patients. Inhibition of LRG-1 or its downstream pathway could be a potential therapeutic target for the treatment of PDAC.

Keywords: Biomarker; Epidermal growth factor receptor (EGFR); LRG-1; Pancreatic ductal adenocarcinoma; p38.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / pathology*
  • Disease Progression
  • ErbB Receptors / metabolism
  • Female
  • Glycoproteins / metabolism*
  • Heterografts
  • Humans
  • MAP Kinase Signaling System / physiology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Retrospective Studies


  • Biomarkers, Tumor
  • Glycoproteins
  • LRG1 protein, human
  • EGFR protein, human
  • ErbB Receptors