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Mangenese superoxide dismutase (MnSOD) promotes stem‐like cell phenotypes in breast cancer
Author(s) -
He Chenxia,
Hart Peter,
Fricano Kristine,
Vargas Micaela,
Thieraud Kraig,
Abreu Andre Luelsdorf,
Bonini Marcelo
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.809.15
Subject(s) - sox2 , homeobox protein nanog , cancer stem cell , cancer research , stem cell , biology , metastasis , stem cell marker , population , cancer cell , reprogramming , cancer , immunology , medicine , cell , transcription factor , microbiology and biotechnology , induced pluripotent stem cell , genetics , environmental health , gene , embryonic stem cell
It is becoming increasingly clear that a small subpopulation of cells within tumors displaying stem cell characteristics drive tumor resistance to therapy, recurrence and metastasis. These cells are generally referred to as cancer stem cells (CSC). Reactive oxygen species (ROS) are active signaling metabolites produced in mitochondria and to a significance extent serve as determinants of cellular reprogramming to stemness. In our study we found that a primary ROS detoxifying enzyme MnSOD is dysregulated in breast cancer and that higher levels of MnSOD expression are associated with lowest survival odds in patients with tumors displaying a MnSOD high molecular signature. In primary breast tumor cell line MCF7, overexpression of MnSOD leads to higher expression of stemness markers (Oct4, Sox2 and Nanog), increased stem cell population, and upregulation of cancer stem cell regulator hypoxia‐induced factor HIF2α transcription factor. Also, MCF7 cells which are amongst the least invasive breast cancer cell lines show significantly enhanced colony forming capacity and invasiveness ex vivo , and metastatic potential in mice. Silencing of HIF2α reversed the effect of MnSOD ectopic expression in MCF7. Altogether our results indicate that there is a MnSOD high /HIF2α phenotype in breast cancer that displays stem‐like cell characteristics which may be involved in treatment resistance and metastatic recurrence in a subgroup of patients displaying MnSOD high tumors. Support or Funding Information This research supported by the U.S. Department of Defense (ARO #61758‐LS) to M.G.B, the NCRR/NIH (S10RR027848) to M.G.B.