Cytoglobin in tumor hypoxia: novel insights into cancer suppression

Abstract

Emerging new and intriguing roles of cytoglobin (Cygb) have attracted considerable attention of cancer researchers in recent years. Hypoxic upregulation of Cygb as well as its altered expression in various human cancers suggest another possible role of this newly discovered globin in tumor cell response under low oxygen tension. Since tumor hypoxia is strongly associated with malignant progression of disease and poor treatment response, it constitutes an area of paramount importance for rational design of cancer selective therapies. However, the mechanisms involved during this process are still elusive. This review outlines the current understanding of Cygb's involvement in tumor hypoxia and discusses its role in tumorigenesis. A better perception of Cygb in tumor hypoxia response is likely to open novel perspectives for future tumor therapy.

Evaluating the Association of Heme and Heme Metabolites with Lung Cancer Bioenergetics and Progression

“…Cytoglobin is able to bind oxygen, and it is known to regulate oxygen levels in cancer cells during hypoxia [19]. Cytoglobin is a stress-related gene, and its expression level is upregulated during oxidative stress in tumors [19]. Our data has shown that the level of cytoglobin is increased many folds in NSCLC cells and tumor xenografts ( Figure 2 C and 2D).…”

“…In cancer cells and tumor xenografts, an increase in heme synthesis and uptake occurs concomitantly with increased levels of hemoproteins such as cytoglobin ( Figure 2C), cytochrome c, Cox-2 and CYP1B1. Cytoglobin is able to bind oxygen, and it is known to regulate oxygen levels in cancer cells during hypoxia [19]. Cytoglobin is a stress-related gene, and its expression level is upregulated during oxidative stress in tumors [19].…”

Cytoglobin ameliorates the stemness of hepatocellular carcinoma via coupling oxidative‐nitrosative stress signals

“…Hypoxia induces Cygb upregulation and protects cancer cells from ONS-induced apoptosis. [23][24][25][26] Thus the anti-tumor effect and underlying mechanism of Cygb need to be further explored.…”

“…Interestingly, Cygb appears to confer intriguing protective properties in tumor cell against oxidative stress injury. Hypoxia induces Cygb upregulation and protects cancer cells from ONS‐induced apoptosis . Thus the anti‐tumor effect and underlying mechanism of Cygb need to be further explored.…”

Redox and Peroxidase Activities of the Hemoglobin Superfamily: Relevance to Health and Disease

“…However, this is a double-edged-sword as Cygb appears to function not only as a tumor suppressor but also protects hypoxic tumors against therapy. The potential role of Cygb in cancer suppression and hypoxic tumor protection has been recently reviewed (15).…”