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PTTG1: a Unique Regulator of Stem/Cancer Stem Cells in the Ovary and Ovarian Cancer

  • Seema Parte
  • Irma Virant-Klun
  • Manish Patankar
  • Surinder K. Batra
  • Alex Straughn
  • Sham S. KakarEmail author
Article
  • 196 Downloads

Abstract

Origin of cancer stem cells (CSCs) and mechanisms by which oncogene PTTG1 contributes to tumor progression via CSCs is not known. Ovarian CSCs exhibit characteristics of self-renewal, tumor-initiation, growth, differentiation, drug resistance, and tumor relapse. A common location of putative origin, namely the ovarian surface epithelium, is shared between the normal stem and CSC compartments. Existence of ovarian stem cells and their co-expression with CSC signatures suggests a strong correlation between origin of epithelial cancer and CSCs. We hereby explored a putative oncogene PTTG1 (Securin), reported to be overexpressed in various tumors, including ovarian. We report a previously overlooked role of PTTG1 as a marker of CSCs thereby modulating CSC, germline, and stemness-related genes. We further characterized PTTG1’s ability to regulate (cancer) stem cell-associated self-renewal and epithelial-mesenchymal transition pathways. Collectively, the data sheds light on a potential target expressed during ovarian tumorigenesis and metastatically disseminated ascites CSCs in the peritoneal cavity. Present study highlights this unconventional, under-explored role of PTTG1 in regulation of stem and CSC compartments in ovary, ovarian cancer and ascites and highlights it as a potential candidate for developing CSC specific targeted therapeutics.

Keywords

Oncogene PTTG1 Securin Cancer stem cells Ovary Stem cells Ovarian cancer 

Notes

Acknowledgements

The authors would like to thank the Confocal Microscopy facility (University of Louisville) for allowing extensive use of the confocal microscope and Dr. V. Jala (Department of Microbiology & Immunology, University of Louisville) for his technical help during confocal microscopy.

Authors’ Contributions

SSK conceived and designed the work. SSK, IVK, MP, and ARS performed the experiments and data acquisition. SSK and ARS quantified data and performed statistical analyses. SP provided intellectual inputs for the study, data analysis and interpretation and prepared the first to final drafts of the manuscript with SSK. SP, IVK, and SSK wrote the manuscript and all authors (SP, ARS, IVK, MP, SKB, SSK) edited the manuscript and approved the final version.

Funding

This study was funded by a grant from NIH/NCI UO1CA2177798 (SKB, SSK) and T32HL134644 (SSK).

Compliance with Ethical Standards

Competing Interests

The authors declare that they have no competing interest.

Disclaimer Note

The authors regret if they have missed quoting any work wherever they should have, due to space constraints or oversight. The overwhelming information available in the knowledge base is truly appreciated by us as we humbly join the war against cancer with this publication.

Supplementary material

12015_2019_9911_MOESM1_ESM.docx (15 kb)
ESM 1 (DOCX 14 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PhysiologyUniversity of LouisvilleLouisvilleUSA
  2. 2.James Graham Brown Cancer CenterUniversity of LouisvilleLouisvilleUSA
  3. 3.Department of Obstetrics and GynecologyUniversity Medical Centre LjubljanaLjubljanaSlovenia
  4. 4.Department of Obstetrics and GynecologyUniversity of Wisconsin-MadisonMadisonUSA
  5. 5.Department of Biochemistry and Molecular BiologyUniversity of NebraskaOmahaUSA

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