The Role of Cytoglobin in Cancer

Abstract

Cytoglobin (Cygb) is a new member of the globin protein family, following the discovery of other
globin proteins such as hemoglobin (Hb), myoglobin (Mb), and neuroglobin (Ngb). In 2001, Kawada
et al. identified Cygb in hepatic stellate cells (HSCs) that play an important role in the repair of
damaged liver cell tissue, hence the name stellate cell activation-associated protein (STAP). Cygb
has a more universal role than Hb, Mb, and Ngb, and is expressed throughout mammalian tissues.
Cygb is a globin with 6 coordination bonds (hexacoordinate globin). Cygb has been shown to play
an important role in the normal cell respiratory chain, including oxygen storage, destruction of
reactive oxygen species (ROS), terminal oxidase activity, regulation of fibrogenesis, and regulation
of apoptosis. The role of Cygb in the respiratory process has been studied because it is associated
with the globin family, and because of the upregulation of Cygb during hypoxia, but its specific role
has not been elaborated. Recent research reports that Cygb has several implications for cancer. In
most cancer cells, Cygb expression is upregulated by hypermethylation, suggesting epigenetic
control. In cancer cells, downregulation of Cygb occurs which indicates a possible role as a tumor
suppressor gene. In some malignancies, on the contrary, Cygb upregulation may be associated with
resistance to hypoxia which indicates Cygb has two sides or Janus faces related to its role in cancer
cells.