Skip to main content

Advertisement

Log in

ARK5 is associated with the invasive and metastatic potential of human breast cancer cells

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

To investigate the effects of Akt/ARK5 pathways on the metastatic potential of human breast cancer cells.

Materials and methods

The human ARK5 gene was transfected into MDA-MB-231 cells. Effects of ARK5 on MDA-MB-231 cells were investigated in vitro. The tumorigenicity and spontaneously metastatic capability regulated by ARK5 were determined using an orthotopic xenograft tumor model.

Results

ARK5 enhanced the invasive and metastatic potential of MDA-MB-231 cells under regulation by Akt. The enhancement was associated with increasing MMP-2, MMP-9, and MT1-MMP expression. The results were further demonstrated by RNA interference experiment. In an in vivo study, we also demonstrated that ARK5-transfected breast cancer cells grew faster and had more pulmonary metastases than its parental counterparts.

Conclusion

ARK5 led to a more invasive phenotype and metastatic potential in human breast cancer dependent on Akt.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Cavdar Z, Canda AE, Terzi C, Sarioglu S, Fuzun M, Oktay G (2011) Role of gelatinases (Mmp-2 and Mmp-9), vascular endothelial growth factor (Vegf) and endostatin on clinicopathological behavior of rectal cancer. Colorectal Dis 13:154–160

    Article  PubMed  CAS  Google Scholar 

  • Chang XZ, Li DQ, Hou YF, Wu J, Lu JS, Di GH, Jin W, Ou ZL, Shen ZZ, Shao ZM (2007a) Identification of the functional role of peroxiredoxin 6 in the progression of breast cancer. Breast Cancer Res 9:R76

    Article  PubMed  Google Scholar 

  • Chang XZ, Wang ZM, Yu JM, Tian FG, Jin W, Zhang Y, Yu J, Li LF, Liu XF, Li ZW, Shao ZM (2007b) Isolation of a human gallbladder cancer cell clone with high invasive phenotype in vitro and metastatic potential in orthotopic model and inhibition of its invasiveness by heparanase antisense oligodeoxynucleotides. Clin Exp Metastasis 24:25–38

    Article  PubMed  CAS  Google Scholar 

  • Chang XZ, Li DQ, Hou YF, Wu J, Lu JS, Di GH, Jin W, Ou ZL, Shen ZZ, Shao ZM (2008) Identification of the functional role of AF1Q in the progression of breast cancer. Breast Cancer Res Treat 111:65–78

    Article  PubMed  CAS  Google Scholar 

  • Chang XZ, Yu J, Zhang XH, Yin J, Wang T, Cao XC (2009) Enhanced expression of trophinin promotes invasive and metastatic potential of human gallbladder cancer cells. J Cancer Res Clin Oncol 135:581–590

    Article  PubMed  CAS  Google Scholar 

  • Ekstrand AI, Jonsson M, Lindblom A, Borg A, Nilbert M (2010) Frequent alterations of the PI3K/AKT/mTOR pathways in hereditary nonpolyposis colorectal cancer. Fam Cancer 9:125–129

    Article  PubMed  CAS  Google Scholar 

  • Fisher JS, Ju JS, Oppelt PJ, Smith JL, Suzuki A, Esumi H (2005) Muscle contractions, AICAR, and insulin cause phosphorylation of an AMPK-related kinase. Am J Physiol Endocrinol Metab 289:E986–E992

    Article  PubMed  CAS  Google Scholar 

  • Kusakai G, Suzuki A, Ogura T, Kaminishi M, Esumi H (2004a) Strong association of ARK5 with tumor invasion and metastasis. J Exp Clin Cancer Res 23:263–268

    PubMed  CAS  Google Scholar 

  • Kusakai G, Suzuki A, Ogura T, Miyamoto S, Ochiai A, Kaminishi M, Esumi H (2004b) ARK5 expression in colorectal cancer and its implications for tumor progression. Am J Pathol 164:987–995

    Article  PubMed  CAS  Google Scholar 

  • Li B, Tsao SW, Li YY, Wang X, Ling MT, Wong YC, He QY, Cheung AL (2009) Id-1 promotes tumorigenicity and metastasis of human esophageal cancer cells through activation of PI3 K/AKT signaling pathway. Int J Cancer 125:2576–2585

    Article  PubMed  CAS  Google Scholar 

  • Morito N, Yoh K, Fujioka Y, Nakano T, Shimohata H, Hashimoto Y, Yamada A, Maeda A, Matsuno F, Hata H et al (2006) Overexpression of c-Maf contributes to T-cell lymphoma in both mice and human. Cancer Res 66:812–819

    Article  PubMed  CAS  Google Scholar 

  • Niesler CU, Myburgh KH, Moore F (2007) The changing AMPK expression profile in differentiating mouse skeletal muscle myoblast cells helps confer increasing resistance to apoptosis. Exp Physiol 92:207–217

    Article  PubMed  CAS  Google Scholar 

  • Nteliopoulos G, Marley SB, Gordon MY (2009) Influence of PI-3K/Akt pathway on Wnt signalling in regulating myeloid progenitor cell proliferation. Evidence for a role of autocrine/paracrine Wnt regulation. Br J Haematol 146:637–651

    Article  PubMed  CAS  Google Scholar 

  • Ohta T, Isobe M, Takahashi T, Saitoh-Sekiguchi M, Motoyama T, Kurachi H (2009) The Akt and ERK activation by platinum-based chemotherapy in ovarian cancer is associated with favorable patient outcome. Anticancer Res 29:4639–4647

    PubMed  CAS  Google Scholar 

  • Simon PO Jr, McDunn JE, Kashiwagi H, Chang K, Goedegebuure PS, Hotchkiss RS, Hawkins WG (2009) Targeting AKT with the proapoptotic peptide, TAT-CTMP: a novel strategy for the treatment of human pancreatic adenocarcinoma. Int J Cancer 125:942–951

    Article  PubMed  CAS  Google Scholar 

  • Suzuki A, Kusakai G, Kishimoto A, Lu J, Ogura T, Esumi H (2003a) ARK5 suppresses the cell death induced by nutrient starvation and death receptors via inhibition of caspase 8 activation, but not by chemotherapeutic agents or UV irradiation. Oncogene 22:6177–6182

    Article  PubMed  CAS  Google Scholar 

  • Suzuki A, Kusakai G, Kishimoto A, Lu J, Ogura T, Lavin MF, Esumi H (2003b) Identification of a novel protein kinase mediating Akt survival signaling to the ATM protein. J Biol Chem 278:48–53

    Article  PubMed  CAS  Google Scholar 

  • Suzuki A, Kusakai G, Kishimoto A, Shimojo Y, Miyamoto S, Ogura T, Ochiai A, Esumi H (2004a) Regulation of caspase-6 and FLIP by the AMPK family member ARK5. Oncogene 23:7067–7075

    Article  PubMed  CAS  Google Scholar 

  • Suzuki A, Lu J, Kusakai G, Kishimoto A, Ogura T, Esumi H (2004b) ARK5 is a tumor invasion-associated factor downstream of Akt signaling. Mol Cell Biol 24:3526–3535

    Article  PubMed  CAS  Google Scholar 

  • Suzuki A, Iida S, Kato-Uranishi M, Tajima E, Zhan F, Hanamura I, Huang Y, Ogura T, Takahashi S, Ueda R et al (2005) ARK5 is transcriptionally regulated by the Large-MAF family and mediates IGF-1-induced cell invasion in multiple myeloma: ARK5 as a new molecular determinant of malignant multiple myeloma. Oncogene 24:6936–6944

    Article  PubMed  CAS  Google Scholar 

  • Yan W, Fu Y, Tian D, Liao J, Liu M, Wang B, Xia L, Zhu Q, Luo M (2009) PI3 kinase/Akt signaling mediates epithelial-mesenchymal transition in hypoxic hepatocellular carcinoma cells. Biochem Biophys Res Commun 382:631–636

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported in part by the Grant from Tianjin Health Administration Science Foundation (No. 2010KZ72) and Tianjin Medical University Cancer Institute and Hospital Science Foundation (No.07B05).

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Xin-Zhong Chang or Xu-Chen Cao.

Additional information

Xin-Zhong Chang, Jie Yu and Hai-Yin Liu contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chang, XZ., Yu, J., Liu, HY. et al. ARK5 is associated with the invasive and metastatic potential of human breast cancer cells. J Cancer Res Clin Oncol 138, 247–254 (2012). https://doi.org/10.1007/s00432-011-1102-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-011-1102-1

Keywords

Navigation