Journal of Breast Cancer

Korean Breast Cancer Society (한국유방암학회)
권호 표지
DOI QR코드

DOI QR Code

Significance of Vesicle-Associated Membrane Protein 8 Expression in Predicting Survival in Breast Cancer

  • Yuan, Mengci (Division of Breast Surgery, Department of Surgical Oncology, Research Unit of General Surgery, The First Affiliated Hospital of China Medical University) ;
  • Liao, Jianhua (Department of General Surgery, Zhejiang Hospital) ;
  • Luo, Ji (Division of Breast Surgery, Department of Surgical Oncology, Research Unit of General Surgery, The First Affiliated Hospital of China Medical University) ;
  • Cui, Mengyao (Division of Breast Surgery, Department of Surgical Oncology, Research Unit of General Surgery, The First Affiliated Hospital of China Medical University) ;
  • Jin, Feng (Division of Breast Surgery, Department of Surgical Oncology, Research Unit of General Surgery, The First Affiliated Hospital of China Medical University)
  • Received : 2018.01.06
  • Accepted : 2018.09.21
  • Published : 2018.12.31
⟨ Previous Next ⟩

Abstract

Purpose: Vesicle-associated membrane protein 8 (VAMP8) is a soluble N-ethylmaleimide-sensitive factor receptor protein that participates in autophagy by directly regulating autophagosome membrane fusion and has been reported to be involved in tumor progression. Nevertheless, the expression and prognostic value of VAMP8 in breast cancer (BC) remain unknown. This study aimed to evaluate the clinical significance and biological function of VAMP8 in BC. Methods: A total of 112 BC samples and 30 normal mammary gland samples were collected. The expression of VAMP8 was assessed in both BC tissues and normal mammary gland tissues via a two-step immunohistochemical detection method. Results: The expression of VAMP8 in BC tissues was significantly higher than that in normal breast tissues. Furthermore, increased VAMP8 expression was significantly correlated with tumor size (p=0.007), lymph node metastasis (p=0.024) and recurrence (p=0.001). Patients with high VAMP8 expression had significantly lower cumulative recurrence-free survival and overall survival (p<0.001 for both) than patients with low VAMP8 expression. In multivariate logistic regression and Cox regression analyses, lymph node metastasis and VAMP8 expression were independent prognostic factors for BC. Conclusion: VAMP8 is significantly upregulated in human BC tissues and can thus be a practical and potentially effective surrogate marker for survival in BC patients.

Keywords

Acknowledgement

Supported by : National Natural Science Foundation of China

References

  1. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin 2016;66:115-32. https://doi.org/10.3322/caac.21338
  2. Dowsett M, Dunbier AK. Emerging biomarkers and new understanding of traditional markers in personalized therapy for breast cancer. Clin Cancer Res 2008;14:8019-26. https://doi.org/10.1158/1078-0432.CCR-08-0974
  3. Peng RW, Abellan E, Fussenegger M. Differential effect of exocytic SNAREs on the production of recombinant proteins in mammalian cells. Biotechnol Bioeng 2011;108:611-20. https://doi.org/10.1002/bit.22986
  4. Lau SK, Boutros PC, Pintilie M, Blackhall FH, Zhu CQ, Strumpf D, et al. Three-gene prognostic classifier for early-stage non small-cell lung cancer. J Clin Oncol 2007;25:5562-9. https://doi.org/10.1200/JCO.2007.12.0352
  5. Hasan N, Hu C. Vesicle-associated membrane protein 2 mediates trafficking of alpha5beta1 integrin to the plasma membrane. Exp Cell Res 2010;316:12-23. https://doi.org/10.1016/j.yexcr.2009.10.007
  6. Zarzynska JM. The importance of autophagy regulation in breast cancer development and treatment. Biomed Res Int 2014;2014:710345.
  7. Chen Y, Meng D, Wang H, Sun R, Wang D, Wang S, et al. VAMP8 facilitates cellular proliferation and temozolomide resistance in human glioma cells. Neuro Oncol 2015;17:407-18. https://doi.org/10.1093/neuonc/nou219
  8. Gomes LR, Terra LF, Wailemann RA, Labriola L, Sogayar MC. $TGF-{\beta}1$ modulates the homeostasis between MMPs and MMP inhibitors through p38 MAPK and ERK1/2 in highly invasive breast cancer cells. BMC Cancer 2012;12:26. https://doi.org/10.1186/1471-2407-12-26
  9. Fang Y, Chen Y, Yu L, Zheng C, Qi Y, Li Z, et al. Inhibition of breast cancer metastases by a novel inhibitor of $TGF{\beta}$ receptor 1. J Natl Cancer Inst 2013;105:47-58. https://doi.org/10.1093/jnci/djs485
  10. Langlands FE, Horgan K, Dodwell DD, Smith L. Breast cancer subtypes: response to radiotherapy and potential radiosensitisation. Br J Radiol 2013;86:20120601. https://doi.org/10.1259/bjr.20120601
  11. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29. https://doi.org/10.3322/caac.20138
  12. Fung C, Lock R, Gao S, Salas E, Debnath J. Induction of autophagy during extracellular matrix detachment promotes cell survival. Mol Biol Cell 2008;19:797-806. https://doi.org/10.1091/mbc.e07-10-1092
  13. Martinet W, Agostinis P, Vanhoecke B, Dewaele M, De Meyer GR. Autophagy in disease: a double-edged sword with therapeutic potential. Clin Sci (Lond) 2009;116:697-712. https://doi.org/10.1042/CS20080508
  14. Santagata S, Hu R, Lin NU, Mendillo ML, Collins LC, Hankinson SE, et al. High levels of nuclear heat-shock factor 1 (HSF1) are associated with poor prognosis in breast cancer. Proc Natl Acad Sci U S A 2011;108:18378-83. https://doi.org/10.1073/pnas.1115031108
  15. Desai S, Liu Z, Yao J, Patel N, Chen J, Wu Y, et al. Heat shock factor 1 (HSF1) controls chemoresistance and autophagy through transcriptional regulation of autophagy-related protein 7 (ATG7). J Biol Chem 2013;288:9165-76. https://doi.org/10.1074/jbc.M112.422071
  16. Lin CJ, Lee CC, Shih YL, Lin TY, Wang SH, Lin YF, et al. Resveratrol enhances the therapeutic effect of temozolomide against malignant glioma in vitro and in vivo by inhibiting autophagy. Free Radic Biol Med 2012;52:377-91. https://doi.org/10.1016/j.freeradbiomed.2011.10.487
  17. Cheng P, Ni Z, Dai X, Wang B, Ding W, Rae Smith A, et al. The novel BH-3 mimetic apogossypolone induces Beclin-1- and ROS-mediated autophagy in human hepatocellular carcinoma [corrected] cells. Cell Death Dis 2013;4:e489. https://doi.org/10.1038/cddis.2013.17
  18. Kim YN, Koo KH, Sung JY, Yun UJ, Kim H. Anoikis resistance: an essential prerequisite for tumor metastasis. Int J Cell Biol 2012;2012:306879.
  19. Degenhardt K, Mathew R, Beaudoin B, Bray K, Anderson D, Chen G, et al. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 2006;10:51-64. https://doi.org/10.1016/j.ccr.2006.06.001
  20. Prietsch RF, Monte LG, da Silva FA, Beira FT, Del Pino FA, Campos VF, et al. Genistein induces apoptosis and autophagy in human breast MCF-7 cells by modulating the expression of proapoptotic factors and oxidative stress enzymes. Mol Cell Biochem 2014;390:235-42. https://doi.org/10.1007/s11010-014-1974-x
  21. Ganley IG, Wong PM, Gammoh N, Jiang X. Distinct autophagosomallysosomal fusion mechanism revealed by thapsigargin-induced autophagy arrest. Mol Cell 2011;42:731-43. https://doi.org/10.1016/j.molcel.2011.04.024
  22. Moreau K, Renna M, Rubinsztein DC. Connections between SNAREs and autophagy. Trends Biochem Sci 2013;38:57-63. https://doi.org/10.1016/j.tibs.2012.11.004
  23. Zhu D, Zhang Y, Lam PP, Dolai S, Liu Y, Cai EP, et al. Dual role of VAMP8 in regulating insulin exocytosis and islet ${\beta}$ cell growth. Cell Metab 2012;16:238-49. https://doi.org/10.1016/j.cmet.2012.07.001
  24. Zhao P, Yang L, Lopez JA, Fan J, Burchfield JG, Bai L, et al. Variations in the requirement for v-SNAREs in GLUT4 trafficking in adipocytes. J Cell Sci 2009;122(Pt 19):3472-80. https://doi.org/10.1242/jcs.047449
  25. Behrendorff N, Dolai S, Hong W, Gaisano HY, Thorn P. Vesicle-associated membrane protein 8 (VAMP8) is a SNARE (soluble N-ethylmaleimidesensitive factor attachment protein receptor) selectively required for sequential granule-to-granule fusion. J Biol Chem 2011;286:29627-34. https://doi.org/10.1074/jbc.M111.265199
  26. von Thun A, Birtwistle M, Kalna G, Grindlay J, Strachan D, Kolch W, et al. ERK2 drives tumour cell migration in three-dimensional microenvironments by suppressing expression of Rab17 and liprin-${\beta}2$. J Cell Sci 2012;125(Pt 6):1465-77. https://doi.org/10.1242/jcs.092916
  27. Diaz-Vera J, Palmer S, Hernandez-Fernaud JR, Dornier E, Mitchell LE, Macpherson I, et al. A proteomic approach to identify endosomal cargoes controlling cancer invasiveness. J Cell Sci 2017;130:697-711. https://doi.org/10.1242/jcs.190835

Cited by

  1. A Humanized Yeast Phenomic Model of Deoxycytidine Kinase to Predict Genetic Buffering of Nucleoside Analog Cytotoxicity vol.10, pp.10, 2018, https://doi.org/10.3390/genes10100770