NF-κB Participates in the Stem Cell Phenotype of Ovarian Cancer Cells

Carolina Gonzalez-Torres, Javier Gaytan-Cervantes, Karla Vazquez-Santillan, Edna Ayerim Mandujano-Tinoco, Gisela Ceballos-Cancino, Alfredo Garcia-Venzor, Cecilia Zampedri, Paulina Sanchez-Maldonado, Raul Mojica-Espinosa, Luis Enrique Jimenez-Hernandez, Vilma Maldonado

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Background NF-κB is a transcription factor involved in cancer stem cells maintenance of many tumors. Little is known about the specific stem-associated upstream regulators of this pathway in ovarian cancer. The Aim of the study was to analyze the role of the canonical and non-canonical NF-κB pathways in stem cells of ovarian cancer cell lines. Methods Stem cells were isolated using sorting cytometry. Western blot and RT-PCR were used to quantify protein and messenger RNA levels. Loss and gain of function assays were performed using siRNAs and dominant-negative proteins, respectively. NF-κB binding activity was measured with a reporter gene assay. The stem phenotype was estimated with clonogenic assays using soft agar, colony formation, ovospheres formation and in vivo tumorigenicity assays. Results The CD44+ subpopulation of SKOV3 ovarian cancer cell line presented higher mRNA levels of key stemness genes, an increased tumorigenic capacity and higher expression of the RelA, RelB and IKKα. When the canonical pathway was inhibited by means of a dominant-negative version of IkBα, the stem cell population was reduced, as shown by a reduced CD44+ subpopulation, a decrease in the expression of the stemness genes and a reduction of the stem phenotype. In addition, IKKα, the main upstream non-canonical kinase, was highly expressed in the CSC population. Accordingly, when IKKα was inhibited using shRNAs, the expression of the stemness genes was reduced. Conclusions This report is the first to show the importance of several elements of both NF-κB pathway in maintaining the ovarian cancer stem cell population.

Original languageEnglish
Pages (from-to)343-351
Number of pages9
JournalArchives of Medical Research
Volume48
Issue number4
DOIs
StatePublished - 1 May 2017
Externally publishedYes

Keywords

  • Canonical pathway
  • IKKα
  • NF-κB
  • Non-canonical pathway
  • Ovarian cancer
  • Stem cell

ASJC Scopus subject areas

  • General Medicine

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