Tumor Biology

, Volume 36, Issue 3, pp 1859–1869 | Cite as

Glucose-regulated protein 78 (GRP78) regulates colon cancer metastasis through EMT biomarkers and the NRF-2/HO-1 pathway

  • Yu-Jia Chang
  • Wei-Yu Chen
  • Chien-Yu Huang
  • Hui-Hsiung Liu
  • Po-Li Wei
Research Article

Abstract

Glucose-regulated protein 78 (GRP78) is a key chaperone and stress response protein. Previous studies have demonstrated that high GRP78 expression may be correlated with cancer progression and therapeutic response. However, the role of GRP78 in the metastasis of colon cancer is unclear. In this study, we used small interfering RNA (siRNA) to knock down GRP78 expression in colon cancer cells (HT-29 and DLD-1 cells). In wound-healing migration assays, we found that GRP78-knockdown (GRP78KD) cells showed better wound-healing ability than control cells. We also found that GRP78KD cells displayed a better migratory ability than control cells in migration and invasion assays. As we further dissected the underlying molecular mechanism, we found that silencing GRP78 may cause an increase in vimentin expression and a decrease in the E-cadherin level, which was correlated with the increase in migratory ability. In addition, we found that GRP78KD may activate the NRF-2/HO-1 pathway, and this activation was also correlated with the increase in cell invasiveness. Furthermore, we examined GRP78 expression in a tissue array and found that the GRP78 expression in metastatic adenocarcinoma in lymph nodes tended to be weaker than that in primary colonic adenocarcinoma. In conclusion, a low level of GRP78 may cause an increase in metastasis ability in colon cancer cells by altering E-cadherin and vimentin expression and activating the NRF-2/HO-1 signaling pathway. Our study demonstrates that low expression of GRP78 may correlate with a high risk of metastasis in colon cancer.

Keywords

GRP78 Metastasis Colon cancer NRF2 HO-1 

Notes

Acknowledgments

This study was supported by grants from the National Science Council (NSC101-2314-B-038-029-MY3 and NSC101-2314-B-038-016-MY3) and MOHW103-TDU-B-212-113001.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Yu-Jia Chang
    • 1
    • 2
    • 3
    • 4
  • Wei-Yu Chen
    • 5
    • 6
  • Chien-Yu Huang
    • 7
    • 8
  • Hui-Hsiung Liu
    • 9
  • Po-Li Wei
    • 2
    • 3
    • 4
    • 10
  1. 1.Graduate Institute of Clinical Medicine, College of MedicineTaipei Medical UniversityTaipeiTaiwan
  2. 2.Department of Surgery, College of MedicineTaipei Medical UniversityTaipeiTaiwan
  3. 3.Division of General Surgery, Department of SurgeryTaipei Medical University HospitalTaipeiTaiwan
  4. 4.Cancer Research CenterTaipei Medical University HospitalTaipeiTaiwan
  5. 5.Department of Pathology, Wan Fang HospitalTaipei Medical UniversityTaipeiTaiwan
  6. 6.Department of Pathology, School of Medicine, College of MedicineTaipei Medical UniversityTaipeiTaiwan
  7. 7.Division of General Surgery, Department of Surgery, Shuang Ho HospitalTaipei Medical UniversityTaipeiTaiwan
  8. 8.Department of Neurosurgery, Shuang Ho HospitalTaipei Medical UniversityTaipeiTaiwan
  9. 9.School of Public Health, College of Public Health and NutritionTaipei Medical UniversityTaipeiTaiwan
  10. 10.Graduate Institute of Cancer Biology and Drug DiscoveryTaipei Medical UniversityTaipeiTaiwan

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