SpringerLink
Log in

Oncogenicity of the transcription factor SOX8 in hepatocellular carcinoma

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

SOX genes play an important role in a number of developmental processes. SOXs have been demonstrated to have potential roles as either tumor suppressors or promoters in various neoplastic tissues depending on the tumor status and type. The aim of this study was to investigate the functional role of SOXs in human cancers. Gene expression changes of SOXs in human hepatocellular carcinoma (HCC) tissues were detected using real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry and compared with those in non-cancerous hepatic tissues. We found by qRT-PCR analysis and immunohistochemistry that the gene SOX8 was significantly upregulated in HCC. Furthermore, we discovered that SOX8 promoted cancer cell proliferation in vitro and that its expression was correlated with elevated β-catenin levels in HCC, whose function was required for the oncogenic effects of SOX8.

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

Access this article

Log in via an institution

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

Similar content being viewed by others

References

  1. Tanaka S, Arii S. Molecular targeted therapies in hepatocellular carcinoma. Semin Oncol. 2012;39(4):486–92.

    Article  PubMed  CAS  Google Scholar 

  2. Vinas A, et al. Map** of DNA sex-specific markers and genes related to sex differentiation in turbot (Scophthalmus maximus). Mar Biotechnol (NY). 2012;14(5):655–63.

    Article  CAS  Google Scholar 

  3. Ng CK, et al. Deciphering the Sox–Oct partner code by quantitative cooperativity measurements. Nucleic Acids Res. 2012;40(11):4933–41.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Coco C, et al. Increased expression of CD133 and reduced dystroglycan expression are strong predictors of poor outcome in colon cancer patients. J Exp Clin Cancer Res. 2012;31:71.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  5. Zhang W, et al. Epigenetic inactivation of the canonical Wnt antagonist SRY-box containing gene 17 in colorectal cancer. Cancer Res. 2008;68(8):2764–72.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  6. Scott EL, Brann DW. Estrogen regulation of Dkk1 and Wnt/beta-catenin signaling in neurodegenerative disease. Brain Res. 2013;1514:63–74.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  7. Laudet V, Stehelin D, Clevers H. Ancestry and diversity of the HMG box superfamily. Nucleic Acids Res. 1993;21(10):2493–501.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  8. Cao JM, et al. High mobility group B proteins regulate mesoderm formation and dorsoventral patterning during zebrafish and Xenopus early development. Mech Dev. 2012;129(9–12):263–74.

    Article  PubMed  CAS  Google Scholar 

  9. Marchetti B, et al. Uncovering novel actors in astrocyte-neuron crosstalk in Parkinson’s disease: the Wnt/beta-catenin signaling cascade as the common final pathway for neuroprotection and self-repair. Eur J Neurosci. 2013;37(10):1550–63.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Hu S, et al. Sox31 is involved in central nervous system anteroposterior regionalization through regulating the organizer activity in zebrafish. Acta Biochim Biophys Sin (Shanghai). 2011;43(5):387–99.

    Article  CAS  Google Scholar 

  11. Aksoy I, et al. Sox transcription factors require selective interactions with Oct4 and specific transactivation functions to mediate reprogramming. Stem Cells. 2013;31(12):2632–46.

    Google Scholar 

  12. Jiang T, et al. The SOX gene family: function and regulation in testis determination and male fertility maintenance. Mol Biol Rep. 2013;40(3):2187–94.

    Article  PubMed  CAS  Google Scholar 

  13. Goding CR. Melanocyte development and malignant melanoma. Forum (Genova). 2000;10(3):176–87.

    CAS  Google Scholar 

  14. Soullier S, et al. Diversification pattern of the HMG and SOX family members during evolution. J Mol Evol. 1999;48(5):517–27.

    Article  PubMed  CAS  Google Scholar 

  15. Argenton F, et al. Ectopic expression and knockdown of a zebrafish sox21 reveal its role as a transcriptional repressor in early development. Mech Dev. 2004;121(2):131–42.

    Article  PubMed  CAS  Google Scholar 

  16. Juarez M, et al. Characterization of the trunk neural crest in the bamboo shark, Chiloscyllium punctatum. J Comp Neurol. 2013;521(14):3303–20.

    Article  PubMed  CAS  Google Scholar 

  17. Lakiza O, et al. SoxE gene duplication and development of the lamprey branchial skeleton: insights into development and evolution of the neural crest. Dev Biol. 2011;359(1):149–61.

    Article  PubMed  CAS  Google Scholar 

  18. Lavery R, et al. Testicular differentiation occurs in absence of R-spondin1 and Sox9 in mouse sex reversals. PLoS Genet. 2012;8(12):e1003170.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. Klaus A, Birchmeier W. Wnt signalling and its impact on development and cancer. Nat Rev Cancer. 2008;8(5):387–98.

    Article  PubMed  CAS  Google Scholar 

  20. Liu Q, et al. Homologues of sox8 and sox10 in the orange-spotted grouper Epinephelus coioides: sequences, expression patterns, and their effects on cyp19a1a promoter activities in vitro. Comp Biochem Physiol B: Biochem Mol Biol. 2012;163(1):86–95.

    Article  CAS  Google Scholar 

  21. Baarsma HA, et al. Activation of WNT/beta-catenin signaling in pulmonary fibroblasts by TGF-beta(1) is increased in chronic obstructive pulmonary disease. PLoS ONE. 2011;6(9):e25450.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  22. Vijayakumar S, et al. High-frequency canonical Wnt activation in multiple sarcoma subtypes drives proliferation through a TCF/beta-catenin target gene, CDC25A. Cancer Cell. 2011;19(5):601–12.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Kormish JD, Sinner D, Zorn AM. Interactions between SOX factors and Wnt/beta-catenin signaling in development and disease. Dev Dyn. 2010;239(1):56–68.

    PubMed Central  PubMed  CAS  Google Scholar 

  24. Korbut E, Ptak-Belowska A, Brzozowski T. Mechanisms promoting physiological cells progression into tumorigenesis. J Physiol Pharmacol. 2012;63(6):565–70.

    PubMed  CAS  Google Scholar 

  25. Baylin SB, Ohm JE. Epigenetic gene silencing in cancer—a mechanism for early oncogenic pathway addiction? Nat Rev Cancer. 2006;6(2):107–16.

    Article  PubMed  CAS  Google Scholar 

  26. L’Episcopo F, et al. Reactive astrocytes and Wnt/beta-catenin signaling link nigrostriatal injury to repair in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease. Neurobiol Dis. 2011;41(2):508–27.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Bafico A, et al. An autocrine mechanism for constitutive Wnt pathway activation in human cancer cells. Cancer Cell. 2004;6(5):497–506.

    Article  PubMed  CAS  Google Scholar 

  28. Liu F, Millar SE. Wnt/beta-catenin signaling in oral tissue development and disease. J Dent Res. 2010;89(4):318–30.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Ms. Min Ding, Dr. Yumin Chen and Dr. Melissa Cruz of Institute of Shanghai Springermedia for a critical review of the manuscript and the scholar services of After Tumor technology (AfterTumor.com). This work was supported by Foundation of Science Technology Department of Zhejiang Province, China (No. 2012C23072), Natural Science Foundation of Zhejiang Province, China (No. Y2091061), Medical and health science and technology Foundation of Zhejiang Province, China (No. 2013KYA170) and Foundation of Science Technology Department of Hangzhou, Zhejiang Province, China (No. 20110733Q04).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 310018, Zhejiang, China

    Siquan Zhang, Cong Zhu, Limin Zhu, Ting Ji & **anfeng Ding

  2. **xi Hospital of Hang Zhou, Hangzhou, 310023, Zhejiang, China

    Siquan Zhang, Huafeng Liu, Shourong Liu, Nianbo Zhao, **g Wu, **aoxiao Huang, Yujuan Zhang & Jie **

  3. Zhejiang Institute of Microbiology, Hangzhou, 310012, Zhejiang, China

    Cong Zhu

Authors
  1. Siquan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cong Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Limin Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Huafeng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shourong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nianbo Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. **g Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. **aoxiao Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yujuan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jie **
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ting Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. **anfeng Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to **anfeng Ding.

Additional information

Siquan Zhang and Cong Zhu have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, S., Zhu, C., Zhu, L. et al. Oncogenicity of the transcription factor SOX8 in hepatocellular carcinoma. Med Oncol 31, 918 (2014). https://doi.org/10.1007/s12032-014-0918-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-014-0918-3

Keywords

Search

Navigation