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

Stem Cell Rev Rep. 2019 Dec;15(6):866-879. doi: 10.1007/s12015-019-09911-5.

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: Cancer stem cells; Oncogene; Ovarian cancer; Ovary; PTTG1; Securin; Stem cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Differentiation*
  • Cell Self Renewal*
  • Cells, Cultured
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Ovary / cytology*
  • Ovary / metabolism
  • Securin / genetics
  • Securin / metabolism*

Substances

  • Securin
  • pituitary tumor-transforming protein 1, human