Tumor Biology

, Volume 37, Issue 12, pp 15495–15500 | Cite as

Pituitary tumor-transforming gene 1 regulates invasion of prostate cancer cells through MMP13

  • Yun-Hua Lin
  • Yong Tian
  • Jun-Sheng Wang
  • Yong-Guang Jiang
  • Yong Luo
  • Ya-Tong Chen
Original Article


It is critical to understand the molecular mechanisms underlying the migration and invasiveness of prostate cancer (PC) for improving the outcome of therapy. A relationship of pituitary tumor-transforming gene 1 (Pttg1) and matrix metalloproteinase 13 (MMP13) in PC as well as their roles in the metastases of PC has not been studied. Here, we reported significantly higher levels of Pttg1 and MMP13 in the resected PC specimens, compared to the adjacent normal prostate tissue from the same patient. Interestingly, Pttg1 and MMP13 levels strongly correlated with each other. In vitro, Pttg1 activated MMP13, which determined PC cell invasiveness. However, Pttg1 levels were not significantly affected by MMP13. Furthermore, the Pttg1-activated MMP13 in PC cells was significantly suppressed by inhibition of PI3k/Akt, but not ERK/MAPK or JNK pathways. Together, our data suggest that Pttg1 may increase PC cell metastasis by MMP13, and highlight Pttg1/MMP13 axis as a promising therapeutic target for PC treatment.


Prostate cancer (PC) Pituitary tumor-transforming gene 1 (Pttg1) Cancer metastasis Matrix metalloproteinase 13 (MMP13) PI3k/Akt signaling pathway 


Conflict of interest

The authors declare that they have no competing interests.


  1. 1.
    Saylor PJ. Prostate cancer: the androgen receptor remains front and centre. Nat Rev Clin Oncol. 2013;10:126–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Alva A, Hussain M. The changing natural history of metastatic prostate cancer. Cancer J. 2013;19:19–24.CrossRefPubMedGoogle Scholar
  3. 3.
    Beltran H, Rubin MA. New strategies in prostate cancer: translating genomics into the clinic. Clin Cancer Res. 2013;19:517–23.CrossRefPubMedGoogle Scholar
  4. 4.
    Xin L. Cells of origin for cancer: an updated view from prostate cancer. Oncogene. 2013;32:3655–63.CrossRefPubMedGoogle Scholar
  5. 5.
    Lin R, Feng J, Dong S, Pan R, Zhuang H, Ding Z. Regulation of autophagy of prostate cancer cells by beta-catenin signaling. Cell Physiol Biochem. 2015;35:926–32.CrossRefPubMedGoogle Scholar
  6. 6.
    Li T, Zhao X, Mo Z, Huang W, Yan H, Ling Z, et al. Formononetin promotes cell cycle arrest via downregulation of akt/cyclin d1/cdk4 in human prostate cancer cells. Cell Physiol Biochem. 2014;34:1351–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Gillies K, Wertman J, Charette N, Dupre DJ. Anterograde trafficking of cxcr4 and ccr2 receptors in a prostate cancer cell line. Cell Physiol Biochem. 2013;32:74–85.CrossRefPubMedGoogle Scholar
  8. 8.
    Shin D, Kwon HY, Sohn EJ, Nam MS, Kim JH, Lee JC, et al. Upregulation of death receptor 5 and production of reactive oxygen species mediate sensitization of pc-3 prostate cancer cells to trail induced apoptosis by vitisin a. Cell Physiol Biochem. 2015;36:1151–62.CrossRefPubMedGoogle Scholar
  9. 9.
    Hu Q, Tong S, Zhao X, Ding W, Gou Y, Xu K, et al. Periostin mediates tgf-beta-induced epithelial mesenchymal transition in prostate cancer cells. Cell Physiol Biochem. 2015;36:799–809.CrossRefPubMedGoogle Scholar
  10. 10.
    Chen Q, Cai ZK, Chen YB, Gu M, Zheng DC, Zhou J, et al. Poly r(c) binding protein-1 is central to maintenance of cancer stem cells in prostate cancer cells. Cell Physiol Biochem. 2015;35:1052–61.CrossRefPubMedGoogle Scholar
  11. 11.
    Wang X, Cao X. Regulation of metastasis of pediatric multiple myeloma by mmp13. Tumour Biol. 2014;35:8715–20.CrossRefPubMedGoogle Scholar
  12. 12.
    Ye Y, Zhou X, Li X, Tang Y, Sun Y, Fang J. Inhibition of epidermal growth factor receptor signaling prohibits metastasis of gastric cancer via downregulation of mmp7 and mmp13. Tumour Biol. 2014;35:10891–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Zhang J, Wang S, Lu L, Wei G. Mir99a modulates mmp7 and mmp13 to regulate invasiveness of kaposi’s sarcoma. Tumour Biol. 2014;35:12567–73.CrossRefPubMedGoogle Scholar
  14. 14.
    Yu R, Ren SG, Horwitz GA, Wang Z, Melmed S. Pituitary tumor transforming gene (pttg) regulates placental jeg-3 cell division and survival: evidence from live cell imaging. Mol Endocrinol. 2000;14:1137–46.CrossRefPubMedGoogle Scholar
  15. 15.
    Caporali S, Alvino E, Levati L, Esposito AI, Ciomei M, Brasca MG, et al. Down-regulation of the pttg1 proto-oncogene contributes to the melanoma suppressive effects of the cyclin-dependent kinase inhibitor pha-848125. Biochem Pharmacol. 2012;84:598–611.CrossRefPubMedGoogle Scholar
  16. 16.
    Vlotides G, Eigler T, Melmed S. Pituitary tumor-transforming gene: physiology and implications for tumorigenesis. Endocr Rev. 2007;28:165–86.CrossRefPubMedGoogle Scholar
  17. 17.
    Tfelt-Hansen J, Kanuparthi D, Chattopadhyay N. The emerging role of pituitary tumor transforming gene in tumorigenesis. Clin Med Res. 2006;4:130–7.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Zhang E, Liu S, Xu Z, Huang S, Tan X, Sun C, et al. Pituitary tumor-transforming gene 1 (pttg1) is overexpressed in oral squamous cell carcinoma (oscc) and promotes migration, invasion and epithelial-mesenchymal transition (emt) in scc15 cells. Tumour Biol. 2014;35:8801–11.CrossRefPubMedGoogle Scholar
  19. 19.
    Zhang G, Zhao Q, Yu S, Lin R, Yi X. Pttg1 inhibits tgfbeta signaling in breast cancer cells to promote their growth. Tumour Biol. 2015;36:199–203.CrossRefPubMedGoogle Scholar
  20. 20.
    Huang S, Liao Q, Li L, Xin D. Pttg1 inhibits smad3 in prostate cancer cells to promote their proliferation. Tumour Biol. 2014;35:6265–70.CrossRefPubMedGoogle Scholar
  21. 21.
    Jia W, Lu R, Jia G, Ni M, Xu Z. Expression of pituitary tumor transforming gene (pttg) in human pituitary macroadenomas. Tumour Biol. 2013;34:1559–67.CrossRefPubMedGoogle Scholar
  22. 22.
    Liang CC, Park AY, Guan JL. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2007;2:329–33.CrossRefPubMedGoogle Scholar
  23. 23.
    Wondergem B, Zhang Z, Huang D, Ong CK, Koeman J, Hof DV, et al. Expression of the pttg1 oncogene is associated with aggressive clear cell renal cell carcinoma. Cancer Res. 2012;72:4361–71.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Yun-Hua Lin
    • 1
  • Yong Tian
    • 2
  • Jun-Sheng Wang
    • 1
  • Yong-Guang Jiang
    • 1
  • Yong Luo
    • 1
  • Ya-Tong Chen
    • 1
  1. 1.Department of Urology, Beijing Anzhen HospitalCapital Medical University of ChinaBeijingChina
  2. 2.Institute of BiophysicsChinese Academy of SciencesBeijingChina

Personalised recommendations