Cancer-Associated Fibroblasts Autophagy Enhances Progression of Triple-Negative Breast Cancer Cells

Med Sci Monit. 2017 Aug 12:23:3904-3912. doi: 10.12659/msm.902870.

Abstract

BACKGROUND Cancer-associated fibroblasts (CAFs) are key factors in malignant tumor initiation, progression, and metastasis. However, the effect of CAFs autophagy on triple-negative breast cancer (TNBC) cells is not clear. In this study, the growth effect of TNBC cells regulated by CAFs autophagy was evaluated. MATERIAL AND METHODS CAFs were obtained from invasive TNBC tumors and identified by Western blot and immunofluorescence staining assay. CAFs were co-cultured with TNBC cells, and migration and invasion were evaluated by Matrigel-coated Transwell and Transwell inserts. TNBC cells growth was detected by MTT assay, and epithelial-mesenchymal transition (EMT) regulated by CAFs was evaluated by Western blot assay. RESULTS CAFs were identified by the high expression of α-smooth muscle actin (α-SMA) protein. Autophagy-relevant Beclin 1 and LC3-II/I protein conversion levels in CAFs were higher than those in NFs (P<0.05). TNBC cells migration, invasion, and proliferation levels were significantly improved in the CAFs-conditioned medium (CAFs-CM) group, compared with the other 3 groups (P<0.05). TNBC cells vimentin and N-cadherin protein levels were upregulated and E-cadherin protein level was downregulated in the CAFs-CM group compared with the control group (P<0.05). Further study indicated b-catenin and P-GSK-3β protein levels, which are the key proteins in the Wnt/β-catenin pathway, were upregulated in the CAFs-CM group compared with the control group (P<0.05). CONCLUSIONS Our data demonstrated CAFs autophagy can enhance TNBC cell migration, invasion, and proliferation, and CAFs autophagy can induce TNBC cells to engage in the EMT process through the Wnt/β-catenin pathway.

MeSH terms

  • Actins / analysis
  • Actins / metabolism*
  • Autophagy / drug effects
  • Autophagy / physiology
  • Cadherins / metabolism
  • Cancer-Associated Fibroblasts / drug effects
  • Cancer-Associated Fibroblasts / metabolism*
  • Cancer-Associated Fibroblasts / physiology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / drug effects
  • China
  • Disease Progression
  • Epithelial-Mesenchymal Transition / drug effects
  • Female
  • Fibroblasts / drug effects
  • Humans
  • Myocytes, Smooth Muscle / metabolism
  • Triple Negative Breast Neoplasms / metabolism*
  • Triple Negative Breast Neoplasms / physiopathology
  • Wnt Signaling Pathway / drug effects
  • beta Catenin / drug effects
  • beta Catenin / metabolism

Substances

  • ACTA2 protein, human
  • Actins
  • Cadherins
  • beta Catenin