[go: up one dir, main page]
Skip to main content

Advertisement

SpringerLink
Log in

The oncogenetic role of stanniocalcin 1 in lung adenocarcinoma: a promising serum candidate biomarker for tracking lung adenocarcinoma progression

  • Original Article
  • Published:
Tumor Biology

Abstract

Stanniocalcin 1 (STC1) is reported to functionally participate in the development of several cancers. However, the role of STC1 in the tumorigenesis and progression of lung adenocarcinoma remains to be fully elucidated. Here, we found that the average levels of serum STC1 were 5.47, 5.53, and 6.94 ng/mL (P = 0.0045) in the healthy subjects and patients with lung adenocarcinoma at tumor stages I–II and III–IV according to Union for International Cancer Control (UICC), respectively. Subsequently, the positive correlation between the STC1 expression level in lung adenocarcinoma tissues and tumor stages was confirmed by immunohistochemical staining assay. Additionally, studies in the STC1-overexpressing or STC1-silenced stable cell lines showed that STC1 increased cell proliferation by promoting G1/S transition in cell cycle progression via up-regulating cyclin B1 and cyclin E. Moreover, studies in the STC1-overexpressing or STC1-silenced stable cell lines also showed that STC1 inhibited cell apoptosis by up-regulating the expression of anti-apoptosis proteins Bcl-2 and Bcl-xl and down-regulating the expression of pro-apoptosis proteins Bax, Bak, and Bid via the activation of the ERK and JNK signaling pathway. In addition, neutralization of STC1 with monoclonal antibody significantly increased the apoptosis of A549 cells. Taken together, our findings strongly suggest that elevated expression of STC1 protein at the III–IV stage of lung adenocarcinoma promotes tumorigenesis of lung adenocarcinoma and positively associates with the cancer progression, which may be of potential value as tumor marker in clinical tracking lung adenocarcinoma progression.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Cancer IAfRo. Organization WH: Globocan: estimated cancer incidence, mortality, and prevalence worldwide in 2012. IARC, 2014.

  2. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.

    Article  PubMed  Google Scholar 

  3. Wagner G, Hampong M, Park C, Copp D. Purification, characterization, and bioassay of teleocalcin, a glycoprotein from salmon corpuscles of Stannius. Gen Comp Endocrinol. 1986;63:481–91.

    Article  CAS  PubMed  Google Scholar 

  4. Fujiwara Y, Sugita Y, Nakamori S, Miyamoto A, Shiozaki K, Nagano H, et al. Assessment of Stanniocalcin-1 mRNA as a molecular marker for micrometastases of various human cancers. Int J Oncol. 2000;16:799–804.

    CAS  PubMed  Google Scholar 

  5. Yoshiko Y, Aubin JE. Stanniocalcin 1 as a pleiotropic factor in mammals. Peptides. 2004;25:1663–9.

    Article  CAS  PubMed  Google Scholar 

  6. Chang AC-M, Janosi J, Hulsbeek M, de Jong D, Jeffrey KJ, Noble JR, et al. A novel human cDNA highly homologous to the fish hormone stanniocalcin. Mol Cell Endocrinol. 1995;112:241–7.

    Article  CAS  PubMed  Google Scholar 

  7. Varghese R, Wong CK, Deol H, Wagner GF, DiMattia GE. Comparative analysis of mammalian stanniocalcin genes 1. Endocrinology. 1998;139:4714–25.

    CAS  Google Scholar 

  8. Kahn J, Mehraban F, Ingle G, Xin X, Bryant JE, Vehar G, et al. Gene expression profiling in an in vitro model of angiogenesis. Am J Pathol. 2000;156:1887–900.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kanellis J, Bick R, Garcia G, Truong L, Tsao CC, Etemadmoghadam D, et al. Stanniocalcin-1, an inhibitor of macrophage chemotaxis and chemokinesis. Am J Physiol Renal Physiol. 2004;286:F356–62.

    Article  CAS  PubMed  Google Scholar 

  10. Song G, Dunlap KA, Kim J, Bailey DW, Spencer TE, Burghardt RC, et al. Stanniocalcin 1 is a luminal epithelial marker for implantation in pigs regulated by progesterone and estradiol. Endocrinology. 2009;150:936–45.

    Article  CAS  PubMed  Google Scholar 

  11. Block GJ, Ohkouchi S, Fung F, Frenkel J, Gregory C, Pochampally R, et al. Multipotent stromal cells are activated to reduce apoptosis in part by upregulation and secretion of stanniocalcin‐1. Stem Cells. 2009;27:670–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Du YZ, Gu XH, Li L, Gao F. The diagnostic value of circulating stanniocalcin-1 mRNA in non-small cell lung cancer. J Surg Oncol. 2011;104:836–40.

    Article  CAS  PubMed  Google Scholar 

  13. Joensuu K, Heikkila P, Andersson LC. Tumor dormancy: elevated expression of stanniocalcins in late relapsing breast cancer. Cancer Lett. 2008;265:76–83.

    Article  CAS  PubMed  Google Scholar 

  14. Tohmiya Y, Koide Y, Fujimaki S, Harigae H, Funato T, Kaku M, et al. Stanniocalcin-1 as a novel marker to detect minimal residual disease of human leukemia. Tohoku J Exp Med. 2004;204:125–33.

    Article  CAS  PubMed  Google Scholar 

  15. He LF, Wang TT, Gao QY, Zhao GF, Huang YH, Yu LK, et al. Stanniocalcin-1 promotes tumor angiogenesis through up-regulation of VEGF in gastric cancer cells. J Biomed Sci. 2011;18:39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Pena C, Cespedes MV, Lindh MB, Kiflemariam S, Mezheyeuski A, Edqvist PH, et al. STC1 expression by cancer-associated fibroblasts drives metastasis of colorectal cancer. Cancer Res. 2013;73:1287–97.

    Article  CAS  PubMed  Google Scholar 

  17. Liu G, Yang G, Chang B, Mercado-Uribe I, Huang M, Zheng J, et al. Stanniocalcin 1 and ovarian tumorigenesis. J Natl Cancer Inst. 2010;102:812–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Evans T, Rosenthal ET, Youngblom J, Distel D, Hunt T. Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell. 1983;33:389–96.

    Article  CAS  PubMed  Google Scholar 

  19. Galderisi U, Jori FP, Giordano A. Cell cycle regulation and neural differentiation. Oncogene. 2003;22:5208–19.

    Article  CAS  PubMed  Google Scholar 

  20. Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009;9:153–66.

    Article  CAS  PubMed  Google Scholar 

  21. Tamura S, Oshima T, Yoshihara K, Kanazawa A, Yamada T, Inagaki D, et al. Clinical significance of STC1 gene expression in patients with colorectal cancer. Anticancer Res. 2011;31:325–9.

    CAS  PubMed  Google Scholar 

  22. Zhou H, Li YY, Zhang WQ, Lin D, Zhang WM, Dong WD. Expression of stanniocalcin-1 and stanniocalcin-2 in laryngeal squamous cell carcinoma and correlations with clinical and pathological parameters. PLoS One. 2014;9, e95466.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Murai R, Tanaka M, Takahashi Y, Kuribayashi K, Kobayashi D, Watanabe N. Stanniocalcin-1 promotes metastasis in a human breast cancer cell line through activation of PI3K. Clin Exp Metastasis. 2014;31:787–94.

    Article  CAS  PubMed  Google Scholar 

  24. Ma X, Gu L, Li H, Gao Y, Li X, Shen D, et al. Hypoxia-induced overexpression of stanniocalcin-1 is associated with the metastasis of early stage clear cell renal cell carcinoma. J Transl Med. 2015;13:56.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Shirakawa M, Fujiwara Y, Sugita Y, Moon J-H, Takiguchi S, Nakajima K, et al. Assessment of stanniocalcin-1 as a prognostic marker in human esophageal squamous cell carcinoma. Oncol Rep. 2012;27:940–6.

    CAS  PubMed  Google Scholar 

  26. Weinberg F, Hamanaka R, Wheaton WW, Weinberg S, Joseph J, Lopez M, et al. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci. 2010;107:8788–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. McCudden CR, James KA, Hasilo C, Wagner GF. Characterization of mammalian stanniocalcin receptors mitochondrial targeting of ligand and receptor for regulation of cellular metabolism. J Biol Chem. 2002;277:45249–58.

    Article  CAS  PubMed  Google Scholar 

  28. Bertoli C, Skotheim JM, de Bruin RA. Control of cell cycle transcription during G1 and S phases. Nat Rev Mol Cell Biol. 2013;14:518–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Stein GS, Van Wijnen AJ, Stein JL, Lian JB, Montecino M, Zaidi SK, et al. An architectural perspective of cell‐cycle control at the G1/S phase cell‐cycle transition. J Cell Physiol. 2006;209:706–10.

    Article  CAS  PubMed  Google Scholar 

  30. Canzonieri V, Barzan L, Franchin G, Vaccher E, Talamini R, Sulfaro S, et al. Alteration of G1/S transition regulators influences recurrences in head and neck squamous carcinomas. J Cell Physiol. 2012;227:233–8.

    Article  CAS  PubMed  Google Scholar 

  31. Chang AC, Doherty J, Huschtscha LI, Redvers R, Restall C, Reddel RR, Anderson RL. Stc1 expression is associated with tumor growth and metastasis in breast cancer. Clin Exp Metastasis. 2014:1–13.

  32. Ohtsubo M, Theodoras AM, Schumacher J, Roberts JM, Pagano M. Human cyclin E, a nuclear protein essential for the G1-to-S phase transition. Mol Cell Biol. 1995;15:2612–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Liu Q-X, Wang X-F, Ikeo K, Hirose S, Gehring WJ, Gojobori T. Evolutionarily conserved transcription factor Apontic controls the G1/S progression by inducing cyclin E during eye development. Proc Natl Acad Sci. 2014;111:9497–502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Liu J-J, Chao J-R, Jiang M-C, Ng S-Y, Yen J, Yang-Yen H-F. Ras transformation results in an elevated level of cyclin D1 and acceleration of G1 progression in NIH 3T3 cells. Mol Cell Biol. 1995;15:3654–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Cai F, Chen P, Chen L, Biskup E, Liu Y, Chen P-C, et al. Human RAD6 promotes G1-S transition and cell proliferation through upregulation of cyclin D1 expression. PLoS One. 2014;9, e113727.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Koff A, Giordano A, Desai D, Yamashita K, Harper JW, Elledge S, et al. Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle. Science. 1992;257:1689–94.

    Article  CAS  PubMed  Google Scholar 

  37. Kolupaeva V, Basilico C. Overexpression of cyclin E/CDK2 complexes overcomes FGF-induced cell cycle arrest in the presence of hypophosphorylated Rb proteins. Cell Cycle. 2012;11:2557–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Baumann K. Cell cycle: maintaining centrosome copy number. Nat Rev Mol Cell Biol. 2012;13:542.

    Google Scholar 

  39. Connell-Crowley L, Harper JW, Goodrich D. Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation. Mol Biol Cell. 1997;8:287–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Liang Y-W, Chang C-C, Hung C-M, Chen T-Y, Huang T-Y, Hsu Y-C. Preclinical activity of simvastatin induces cell cycle arrest in G1 via blockade of cyclin D-Cdk4 expression in non-small cell lung cancer (NSCLC). Int J Mol Sci. 2013;14:5806–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lowe SW, Lin AW. Apoptosis in cancer. Carcinogenesis. 2000;21:485–95.

    Article  CAS  PubMed  Google Scholar 

  42. Wong R. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res. 2011;30:87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kim SJ, Ko JH, Yun J-H, Kim J-A, Kim TE, Lee HJ, et al. Stanniocalcin-1 protects retinal ganglion cells by inhibiting apoptosis and oxidative damage. PLoS One. 2013;8, e63749.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Boucher MJ, Morisset J, Vachon PH, Reed JC, Lainé J, Rivard N. MEK/ERK signaling pathway regulates the expression of Bcl‐2, Bcl‐xl, and Mcl‐1 and promotes survival of human pancreatic cancer cells. J Cell Biochem. 2000;79:355–69.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai, 200233, China

    Yu-Zhen Du, Li Li, Hua Liu, Liu-Ping Hu & Feng Gao

  2. Department of Respiration, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

    Xiao-Hua Gu

  3. Department of Cardiothoracic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

    Shao-Fei Cheng

Authors
  1. Yu-Zhen Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao-Hua Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shao-Fei Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Li Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hua Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Liu-Ping Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Feng Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Feng Gao.

Ethics declarations

Funding

This study was funded by research grants from the Shanghai Hospital Development Center (SHDC12013903).

Conflicts of interest

None

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of Research Ethics Committee of Shanghai Sixth People’s Hospital and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Du, YZ., Gu, XH., Cheng, SF. et al. The oncogenetic role of stanniocalcin 1 in lung adenocarcinoma: a promising serum candidate biomarker for tracking lung adenocarcinoma progression. Tumor Biol. 37, 5633–5644 (2016). https://doi.org/10.1007/s13277-015-4431-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-4431-x

Keywords

Search

Navigation