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

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• 作者：Yu-Jia Chang (1) (2) (3) (4)
  Wei-Yu Chen (5) (6)
  Chien-Yu Huang (7) (8)
  Hui-Hsiung Liu (9)
  Po-Li Wei (10) (2) (3) (4)
  
  1. Graduate Institute of Clinical Medicine ; College of Medicine ; Taipei Medical University ; Taipei ; Taiwan
  2. Department of Surgery ; College of Medicine ; Taipei Medical University ; No. 250 ; Wuxing St. ; Taipei ; 11031 ; Taiwan
  3. Division of General Surgery ; Department of Surgery ; Taipei Medical University Hospital ; Taipei ; Taiwan
  4. Cancer Research Center ; Taipei Medical University Hospital ; Taipei ; Taiwan
  5. Department of Pathology ; Wan Fang Hospital ; Taipei Medical University ; Taipei ; Taiwan
  6. Department of Pathology ; School of Medicine ; College of Medicine ; Taipei Medical University ; Taipei ; Taiwan
  7. Division of General Surgery ; Department of Surgery ; Shuang Ho Hospital ; Taipei Medical University ; Taipei ; Taiwan
  8. Department of Neurosurgery ; Shuang Ho Hospital ; Taipei Medical University ; Taipei ; Taiwan
  9. School of Public Health ; College of Public Health and Nutrition ; Taipei Medical University ; Taipei ; Taiwan
  10. Graduate Institute of Cancer Biology and Drug Discovery ; Taipei Medical University ; Taipei ; Taiwan
  
• 关键词：GRP78 ; Metastasis ; Colon cancer ; NRF2 ; HO ; 1
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：36
• 期：3
• 页码：1859-1869
• 全文大小：2,053 KB
• 参考文献：1. Munro, S, Pelham, HR (1986) An Hsp70-like protein in the ER: identity with the 78 kd glucose-regulated protein and immunoglobulin heavy chain binding protein. Cell 46: pp. 291-300 CrossRef
  2. Haas, IG (1994) Bip (grp78), an essential hsp70 resident protein in the endoplasmic reticulum. Experientia 50: pp. 1012-20 CrossRef
  3. Ni, M, Lee, AS (2007) ER chaperones in mammalian development and human diseases. FEBS Lett 581: pp. 3641-51 CrossRef
  4. Pfaffenbach, KT, Lee, AS (2011) The critical role of grp78 in physiologic and pathologic stress. Curr Opin Cell Biol 23: pp. 150-6 CrossRef
  5. Li, J, Lee, AS (2006) Stress induction of GRP78/BiP and its role in cancer. Curr Mol Med 6: pp. 45-54 CrossRef
  6. Fu, Y, Li, J, Lee, AS (2007) GRP78/BiP inhibits endoplasmic reticulum BIK and protects human breast cancer cells against estrogen starvation-induced apoptosis. Cancer Res 67: pp. 3734-40 CrossRef
  7. Wang, Q, He, Z, Zhang, J, Wang, Y, Wang, T, Tong, S (2005) Overexpression of endoplasmic reticulum molecular chaperone grp94 and grp78 in human lung cancer tissues and its significance. Cancer Detect Prev 29: pp. 544-51 CrossRef
  8. Langer, R, Feith, M, Siewert, JR, Wester, HJ, Hoefler, H (2008) Expression and clinical significance of Glucose Regulated Proteins GRP78 (BiP) and GRP94 (GP96) in human adenocarcinomas of the esophagus. BMC Cancer 8: pp. 70 CrossRef
  9. Zheng, HC, Takahashi, H, Li, XH, Hara, T, Masuda, S, Guan, YF (2008) Overexpression of GRP78 and GRP94 are markers for aggressive behavior and poor prognosis in gastric carcinomas. Hum Pathol 39: pp. 1042-9 CrossRef
  10. Xing, X, Lai, M, Wang, Y, Xu, E, Huang, Q (2006) Overexpression of glucose-regulated protein 78 in colon cancer. Clin Chim Acta 364: pp. 308-15 CrossRef
  11. Bifulco, G, Miele, C, Jeso, B, Beguinot, F, Nappi, C, Carlo, C (2012) Endoplasmic reticulum stress is activated in endometrial adenocarcinoma. Gynecol Oncol 125: pp. 220-5 CrossRef
  12. Song, MS, Park, YK, Lee, JH, Park, K (2001) Induction of glucose-regulated protein 78 by chronic hypoxia in human gastric tumor cells through a protein kinase c-epsilon/erk/ap-1 signaling cascade. Cancer Res 61: pp. 8322-30
  13. Park, HR, Ryoo, IJ, Choo, SJ, Hwang, JH, Kim, JY, Cha, MR (2007) Glucose-deprived HT-29 human colon carcinoma cells are sensitive to verrucosidin as a GRP78 down-regulator. Toxicology 229: pp. 253-61 CrossRef
  14. Chiou, JF, Tai, CJ, Huang, MT, Wei, PL, Wang, YH, An, J (2010) Glucose-regulated protein 78 is a novel contributor to acquisition of resistance to sorafenib in hepatocellular carcinoma. Ann Surg Oncol 17: pp. 603-12 CrossRef
  15. Lee, AS (2007) Grp78 induction in cancer: therapeutic and prognostic implications. Cancer Res 67: pp. 3496-9 CrossRef
  16. Chang, YJ, Huang, YP, Li, ZL, Chen, CH (2012) GRP78 knockdown enhances apoptosis via the down-regulation of oxidative stress and Akt pathway after epirubicin treatment in colon cancer DLD-1 cells. PLoS ONE 7: pp. e35123 CrossRef
  17. Kuo LJ, Hung CS, Chen WY, Chang YJ, Wei PL. Glucose-regulated protein 78 silencing down-regulates vascular endothelial growth factor/vascular endothelial growth factor receptor 2 pathway to suppress human colon cancer tumor growth. J Surg Res 2013
  18. Takahashi, H, Wang, JP, Zheng, HC, Masuda, S, Takano, Y (2011) Overexpression of GRP78 and GRP94 is involved in colorectal carcinogenesis. Histol Histopathol 26: pp. 663-71
  19. Hardy, B, Raiter, A, Yakimov, M, Vilkin, A, Niv, Y (2012) Colon cancer cells expressing cell surface GRP78 as a marker for reduced tumorigenicity. Cell Oncol (Dordr) 35: pp. 345-54 CrossRef
  20. Li, Z, Zhang, L, Zhao, Y, Li, H, Xiao, H, Fu, R (2013) Cell-surface GRP78 facilitates colorectal cancer cell migration and invasion. Int J Biochem Cell Biol 45: pp. 987-94 CrossRef
  21. Wang, M, Wey, S, Zhang, Y, Ye, R, Lee, AS (2009) Role of the unfolded protein response regulator GRP78/BiP in development, cancer, and neurological disorders. Antioxid Redox Signal 11: pp. 2307-16 CrossRef
  22. Hirsch, FR, Varella-Garcia, M, Bunn, PA, Maria, MV, Veve, R, Bremmes, RM (2003) Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol 21: pp. 3798-807 CrossRef
  23. Chang, YJ, Chiu, CC, Wu, CH, An, J, Wu, CC, Liu, TZ (2010) Glucose-regulated protein 78 (GRP78) silencing enhances cell migration but does not influence cell proliferation in hepatocellular carcinoma. Ann Surg Oncol 17: pp. 1703-9 CrossRef
  24. Wei PL, Kuo LJ, Huang MT, Ting WC, Ho YS, Wang W, et al. Nicotine enhances colon cancer cell migration by induction of fibronectin. Ann Surg Oncol 2011
  25. Lien YC, Wang W, Kuo LJ, Liu JJ, Wei PL, Ho YS, et al. Nicotine promotes cell migration through alpha7 nicotinic acetylcholine receptor in gastric cancer cells. Ann Surg Oncol 2011
  26. Wei, PL, Kuo, LJ, Wang, W, Lin, FY, Liu, HH, How, T (2012) Silencing of glucose-regulated protein 78 (GRP78) enhances cell migration through the upregulation of vimentin in hepatocellular carcinoma cells. Ann Surg Oncol 19: pp. S572-9 CrossRef
  27. Pan, H, Wang, H, Zhu, L, Mao, L, Qiao, L, Su, X (2013) The role of Nrf2 in migration and invasion of human glioma cell U251. World Neurosurg 80: pp. 363-70 CrossRef
  28. Jemal, A, Siegel, R, Ward, E, Murray, T, Xu, J, Thun, MJ (2007) Cancer statistics, 2007. CA Cancer J Clin 57: pp. 43-66 CrossRef
  29. Parkin, DM, Bray, F, Ferlay, J, Pisani, P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55: pp. 74-108 CrossRef
  30. Hwang, JH, Kim, JY, Cha, MR, Ryoo, IJ, Choo, SJ, Cho, SM (2008) Etoposide-resistant HT-29 human colon carcinoma cells during glucose deprivation are sensitive to piericidin A, a GRP78 down-regulator. J Cell Physiol 215: pp. 243-50 CrossRef
  31. Luo, B, Lee, AS (2013) The critical roles of endoplasmic reticulum chaperones and unfolded protein response in tumorigenesis and anticancer therapies. Oncogene 32: pp. 805-18 CrossRef
  32. Perez-Moreno, M, Jamora, C, Fuchs, E (2003) Sticky business: orchestrating cellular signals at adherens junctions. Cell 112: pp. 535-48 CrossRef
  33. Perl, AK, Wilgenbus, P, Dahl, U, Semb, H, Christofori, G (1998) A causal role for e-cadherin in the transition from adenoma to carcinoma. Nature 392: pp. 190-3 CrossRef
  34. Wei, PL, Chang, YJ, Ho, YS, Lee, CH, Yang, YY, An, J (2009) Tobacco-specific carcinogen enhances colon cancer cell migration through alpha7-nicotinic acetylcholine receptor. Ann Surg 249: pp. 978-85 CrossRef
  35. Hur K, Toiyama Y, Takahashi M, Balaguer F, Nagasaka T, Koike J, et al. MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis. Gut 2012
  36. Lu, MH, Huang, CC, Pan, MR, Chen, HH, Hung, WC (2012) Prospero homeobox 1 promotes epithelial鈥搈esenchymal transition in colon cancer cells by inhibiting E-cadherin via miR-9. Clin Cancer Res 18: pp. 6416-25 CrossRef
  37. Eriksson, JE, Dechat, T, Grin, B, Helfand, B, Mendez, M, Pallari, HM (2009) Introducing intermediate filaments: from discovery to disease. J Clin Invest 119: pp. 1763-71 CrossRef
  38. Eckes, B, Dogic, D, Colucci-Guyon, E, Wang, N, Maniotis, A, Ingber, D (1998) Impaired mechanical stability, migration and contractile capacity in vimentin-deficient fibroblasts. J Cell Sci 111: pp. 1897-907
  39. Tsuruta, D, Jones, JC (2003) The vimentin cytoskeleton regulates focal contact size and adhesion of endothelial cells subjected to shear stress. J Cell Sci 116: pp. 4977-84 CrossRef
  40. Ivaska, J (2011) Vimentin: Central hub in EMT induction?. Small GTPases 2: pp. 51-3 CrossRef
  41. Forsyth, CB, Tang, Y, Shaikh, M, Zhang, L, Keshavarzian, A (2010) Alcohol stimulates activation of snail, epidermal growth factor receptor signaling, and biomarkers of epithelial鈥搈esenchymal transition in colon and breast cancer cells. Alcohol Clin Exp Res 34: pp. 19-31 CrossRef
  42. Zhou, J, Yang, J, Li, K, Mo, P, Feng, B, Wang, X (2013) RhoE is associated with relapse and prognosis of patients with colorectal cancer. Ann Surg Oncol 20: pp. 175-82 CrossRef
  43. Prevarskaya, N, Skryma, R, Shuba, Y (2011) Calcium in tumour metastasis: new roles for known actors. Nat Rev Cancer 11: pp. 609-18 CrossRef
  44. Monet, M, Lehen鈥檏yi, V, Gackiere, F, Firlej, V, Vandenberghe, M, Roudbaraki, M (2010) Role of cationic channel TRPV2 in promoting prostate cancer migration and progression to androgen resistance. Cancer Res 70: pp. 1225-35 CrossRef
  45. Yang, S, Zhang, JJ, Huang, XY (2009) Orai1 and STIM1 are critical for breast tumor cell migration and metastasis. Cancer Cell 15: pp. 124-34 CrossRef
  46. Davis, FM, Azimi, I, Faville, RA, Peters, AA, Jalink, K, Putney, JW (2014) Induction of epithelial鈥搈esenchymal transition (EMT) in breast cancer cells is calcium signal dependent. Oncogene 33: pp. 2307-16 CrossRef
  47. Ma, R, Sansom, SC (2001) Epidermal growth factor activates store-operated calcium channels in human glomerular mesangial cells. Journal of the American Society of Nephrology : JASN 12: pp. 47-53
  48. Li, WP, Tsiokas, L, Sansom, SC, Ma, R (2004) Epidermal growth factor activates store-operated Ca2+ channels through an inositol 1,4,5-trisphosphate-independent pathway in human glomerular mesangial cells. J Biol Chem 279: pp. 4570-7 CrossRef
  49. Chen, YF, Chiu, WT, Chen, YT, Lin, PY, Huang, HJ, Chou, CY (2011) Calcium store sensor stromal-interaction molecule 1-dependent signaling plays an important role in cervical cancer growth, migration, and angiogenesis. Proc Natl Acad Sci U S A 108: pp. 15225-30 CrossRef
  50. Yang, IH, Tsai, YT, Chiu, SJ, Liu, LT, Lee, HH, Hou, MF (2013) Involvement of STIM1 and Orai1 in EGF-mediated cell growth in retinal pigment epithelial cells. J Biomed Sci 20: pp. 41 CrossRef
  51. Lai, W, Liu, L, Zeng, Y, Wu, H, Xu, H, Chen, S (2013) KCNN4 channels participate in the EMT induced by PRL-3 in colorectal cancer. Med Oncol 30: pp. 566 CrossRef
  52. Maines, MD (2004) The heme oxygenase system: past, present, and future. Antioxid Redox Signal 6: pp. 797-801 CrossRef
  53. Becker, JC, Fukui, H, Imai, Y, Sekikawa, A, Kimura, T, Yamagishi, H (2007) Colonic expression of heme oxygenase-1 is associated with a better long-term survival in patients with colorectal cancer. Scand J Gastroenterol 42: pp. 852-8 CrossRef
  54. Kang, KA, Maeng, YH, Zhang, R, Yang, YR, Piao, MJ, Kim, KC (2012) Involvement of heme oxygenase-1 in Korean colon cancer. Tumour Biol 33: pp. 1031-8 CrossRef
  55. Kensler, TW, Wakabayashi, N, Biswal, S (2007) Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol 47: pp. 89-116 CrossRef
  56. Ma, Q, He, X (2012) Molecular basis of electrophilic and oxidative defense: promises and perils of nrf2. Pharmacol Rev 64: pp. 1055-81 CrossRef
  57. Singh, A, Misra, V, Thimmulappa, RK, Lee, H, Ames, S, Hoque, MO (2006) Dysfunctional KEAP1鈥揘RF2 interaction in non-small-cell lung cancer. PLoS Med 3: pp. e420 CrossRef
  58. Shibata T, Kokubu A, Gotoh M, Ojima H, Ohta T, Yamamoto M, et al. Genetic alteration of Keap1 confers constitutive Nrf2 activation and resistance to chemotherapy in gallbladder cancer. Gastroenterology 2008;135:1358鈥?8, 1368 e1351-1354.
  59. Akhdar, H, Loyer, P, Rauch, C, Corlu, A, Guillouzo, A, Morel, F (2009) Involvement of Nrf2 activation in resistance to 5-fluorouracil in human colon cancer HT-29 cells. Eur J Cancer 45: pp. 2219-27 CrossRef
  60. Hu, T, Yao, Y, Yu, S, Guo, H, Han, L, Wang, W (2013) Clinicopathologic significance of CXCR4 and Nrf2 in colorectal cancer. J Biomed Res 27: pp. 283-90 CrossRef
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

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.