Skip to main content

Advertisement

SpringerLink
Log in

Expression of cellular apoptosis susceptibility (CAS) in the human testis and testicular germ cell tumors

  • Short Communication
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Testicular germ cell tumors are the most frequent malignancies found in men between 15 and 44 years old. Although cellular apoptosis susceptibility (CAS) was demonstrated to be upregulated in breast cancer and colon cancer, the expression of CAS in the human testis and testicular germ cell tumors remained elusive. In the present study, CAS-positive signals were detected in the normal testicular tissues, cancer adjacent normal testicular tissues, seminoma, yolk sac tumor, and teratoma. Interestingly, the expression level of CAS in testicular germ cell tumors (TGCTs) (but not seminoma) was significantly lower than that of human testicular tissues and cancer adjacent normal testicular tissues, suggesting that decreased CAS contributed to the progression of TGCTs. Notably, the expression of CAS in seminoma was significantly higher than that of in the non-seminomas, consistent with the results from TCGA database. Furthermore, the localization of CAS is mainly restricted in the nucleus in the lesions of normal human testicular tissue and cancer adjacent normal testicular tissue. Although the expression of CAS was not significantly different between normal testicular tissue and seminoma, CAS was more enriched in cytoplasm in seminoma compared to the normal, cancer adjacent tissue and other types of TGCTs. The current results demonstrated reduced expression of CAS in the human testicular germ cell tumors and the CAS translocation from the nuclear to cytoplasm in seminoma, thereby supporting a possible role in normal testis function and in the development of seminoma.

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

References

  1. Cheng L, Albers P, Berney DM, Feldman DR, Daugaard G, Gilligan T, Looijenga LHJ. Testicular cancer. Nat Rev Dis Primers. 2018;4:29.

    Article  Google Scholar 

  2. Diez-Torre A, Silvan U, Wever OD, Bruyneel E. Germinal tumor invasion and the role of the testicular stroma. Int J Dev Biol. 2004;48:545–57.

    Article  CAS  Google Scholar 

  3. Jiang MC. CAS (CSE1L) signaling pathway in tumor progression and its potential as a biomarker and target for targeted therapy. Tumour Biol. 2016;37:13077–90.

    Article  CAS  Google Scholar 

  4. Tanaka T, Ohkubo S, Tatsuno I, Prives C. hCAS/CSE1L associates with chromatin and regulates expression of select p53 target genes. Cell. 2007;130:638–50.

    Article  CAS  Google Scholar 

  5. Holzer K, Drucker E, Oliver S, Winkler J, Eiteneuer E, Herpel E, Breuhahn K, Singer S. Cellular apoptosis susceptibility (CAS) is overexpressed in thyroid carcinoma and maintains tumor cell growth: a potential link to the BRAFV600E mutation. Int J Oncol. 2016;48:1679–87.

    Article  CAS  Google Scholar 

  6. Winkler J, Roessler S, Sticht C, DiGuilio AL, Drucker E, Holzer K, Eiteneuer E, Herpel E, Breuhahn K, Gretz N, Schirmacher P, Ori A, Singer S. Cellular apoptosis susceptibility (CAS) is linked to integrin β1 and required for tumor cell migration and invasion in hepatocellular carcinoma. Oncotarget. 2016;7:22883–92.

    PubMed  PubMed Central  Google Scholar 

  7. Zhu J-H, Hong D-F, Song Y-M, Sun L-F, Wang Z-F, Wang J-W. Suppression of cellular apoptosis susceptibility (CSE1L) inhibits proliferation and induces apoptosis in colorectal cancer cells. Asian Pac J Cancer Prev. 2013;14:1017–21.

    Article  Google Scholar 

  8. Pimiento JM, Neill KG, Henderson-Jackson E, Eschrich SA, Chen DT, Husain K, Shibata D, Coppola D, Malafa MP. Knockdown of CSE1L gene in colorectal cancer reduces tumorigenesis in vitro. Am J Pathol. 2016;186:2761–8.

    Article  CAS  Google Scholar 

  9. Liao CF, Luo SF, Li LT, Lin CY, Chen YC, Jiang MC. CSE1L/CAS, the cellular apoptosis susceptibility protein, enhances invasion and metastasis but not proliferation of cancer cells. J Exp Clin Cancer Res. 2008;27:15.

    Article  Google Scholar 

  10. Ouellet V, Guyot MC, Le Page C, Filali-Mouhim A, Lussier C, Tonin PN, Provencher DM, Mes-Masson AM. Tissue array analysis of expression microarray candidates identifies markers associated with tumor grade and outcome in serous epithelial ovarian cancer. Int J Cancer. 2006;119:599–607.

    Article  CAS  Google Scholar 

  11. Yuksel UM, Turker I, Dilek G, Dogan L, Gulcelik MA, Oksuzoglu B. Does CSE1L overexpression affect distant metastasis development in breast cancer? Oncol Res Treat. 2015;38:431–4.

    Article  CAS  Google Scholar 

  12. Yuksel UM, Dilek G, Dogan L, Gulcelik MA, Berberoglu U. The relationship between CSE1L expression and axillary lymph node metastasis in breast cancer. Tumori. 2015;101:194–8.

    Article  CAS  Google Scholar 

  13. Wang C, Zhang J, Fok KL, Tsang LL, Ye M, Liu J, Li F, Zhao AZ, Chan HC, Chen H. CD147 induces epithelial-to-mesenchymal transition by disassembling cellular apoptosis susceptibility protein/E-cadherin/beta-catenin complex in human endometriosis. Am J Pathol. 2018;188:1597–607.

    Article  CAS  Google Scholar 

  14. Chang C-C, Tai C-J, Su T-C, Shen K-H, Lin S-H, Yeh C-M, Yeh K-T, Lin Y-M, Jiang M-C. The prognostic significance of nuclear CSE1L in urinary bladder urothelial carcinomas. Ann Diagn Pathol. 2012;16:362–8.

    Article  Google Scholar 

  15. Mane DR, Kale AD, Belaldavar C. Validation of immunoexpression of tenascin-C in oral precancerous and cancerous tissues using ImageJ analysis with novel immunohistochemistry profiler plugin: an immunohistochemical quantitative analysis. J Oral Maxillofac Pathol: JOMFP. 2017;21:211–7.

    Article  Google Scholar 

  16. Alnabulsi A, Agouni A, Mitra S, Garcia-Murillas I, Carpenter B, Bird S, Murray GI. Cellular apoptosis susceptibility (chromosome segregation 1-like, CSE1L) gene is a key regulator of apoptosis, migration and invasion in colorectal cancer. J Pathol. 2012;228:471–81.

    Article  CAS  Google Scholar 

  17. Lorenzato A, Martino C, Dani N, Oligschlager Y, Ferrero AM, Biglia N, Calogero R, Olivero M, Di Renzo MF. The cellular apoptosis susceptibility CAS/CSE1L gene protects ovarian cancer cells from death by suppressing RASSF1C. FASEB J. 2012;26:2446–56.

    Article  CAS  Google Scholar 

  18. Liao CF, Lin SH, Chen HC, Tai CJ, Chang CC, Li LT, Yeh CM, Yeh KT, Chen YC, Hsu TH, et al. CSE1L, a novel microvesicle membrane protein, mediates Ras-triggered microvesicle generation and metastasis of tumor cells. Mol Med. 2012;18:1269–80.

    Article  CAS  Google Scholar 

  19. Kutay U, Bischoff FR, Kostka S, Kraft R, Görlich D. Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor. Cell. 1997;90:1061–71.

    Article  CAS  Google Scholar 

  20. Dong Q, Li X, Wang CZ, Xu S, Yuan G, Shao W, Liu B, Zheng Y, Wang H, Lei X, et al. Roles of the CSE1L-mediated nuclear import pathway in epigenetic silencing. Proc Natl Acad Sci USA. 2018;115:E4013–22.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported in part by grants from the National Key Research and Development Program of China (Grant No. 2018YFC1003600); National Natural Science Foundation of China (Grant Nos. 81671432, 81871202); Health and Medical Research Fund of Hong Kong (Grant No. 06170476); and the startup R&D funding of Guangdong University of Technology (Grant No. 220418118).

Author information

Author notes

  1. Jianni Liu and Mei Ye contributed equally to this work.

Authors and Affiliations

  1. School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, Guandong Province, People’s Republic of China

    Jianni Liu, Mei Ye, Fanghong Li, Allan Zijian Zhao & Hao Chen

  2. Second Hospital of ShanXi Medical University, Taiyuan, Shanxi, People’s Republic of China

    Jianni Liu, Han Zhang, Xin Wang, Haoran Guo & Kunping Guan

  3. Reproductive Medicine Center of The 306th Hospital of PLA, Beijing, People’s Republic of China

    Ruigang Han

  4. Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, 518035, Guangdong Province, People’s Republic of China

    Yaoting Gui & Xiaofeng Li

Authors
  1. Jianni Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mei Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ruigang Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yaoting Gui
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaofeng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Han Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Haoran Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Fanghong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Allan Zijian Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kunping Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Hao Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HC and KPG conceived and designed the experiments. JNL, RGH, MY, HZ, XW, and HRG performed the experiments and analyzed the data. YTG and XFL collected the TGCTs. FHL and ZJZ gave intellectual advice and revised the manuscript. JNL and HC wrote the paper.

Corresponding authors

Correspondence to Kunping Guan or Hao Chen.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The project was approved by the Ethic Committee of The Second Hospital of Shanxi Medical University.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Hao Chen is the primary corresponding author.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PPTX 185 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, J., Ye, M., Han, R. et al. Expression of cellular apoptosis susceptibility (CAS) in the human testis and testicular germ cell tumors. Med Oncol 36, 61 (2019). https://doi.org/10.1007/s12032-019-1281-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-019-1281-1

Keywords

Search

Navigation