HO-1 Induction in Cancer Progression: A Matter of Cell Adaptation

Abstract

The upregulation of heme oxygenase-1 (HO-1) is one of the most important mechanisms of cell adaptation to stress. Indeed, the redox sensitive transcription factor Nrf2 is the pivotal regulator of HO-1 induction. Through the antioxidant, antiapoptotic, and antinflammatory properties of its metabolic products, HO-1 plays a key role in healthy cells in maintaining redox homeostasis and in preventing carcinogenesis. Nevertheless, several lines of evidence have highlighted the role of HO-1 in cancer progression and its expression correlates with tumor growth, aggressiveness, metastatic and angiogenetic potential, resistance to therapy, tumor escape, and poor prognosis, even though a tumor- and tissue-specific activity has been observed. In this review, we summarize the current literature regarding the pro-tumorigenic role of HO-1 dependent tumor progression as a promising target in anticancer strategy.

Heme Oxygenase 1 in the Nervous System: Does It Favor Neuronal Cell Survival or Induce Neurodegeneration?

“…The overall exacerbation of this protective mechanism can increase cell resistance to many stressors, favoring the gain of an aggressive tumor phenotype [136], but the untimely, prolonged or excessive activation of HO-1 can easily produce a deleterious cytopathic effect. In the nervous system, this mechanism becomes even more complex due to cell–cell interactions, characteristic of brain tissue.…”

HO‐1 downregulation favors BRAFV600 melanoma cell death induced by Vemurafenib/PLX4032 and increases NK recognition

“…Considering the role played by HO-1 induction as key factor limiting the efficacy of tumor therapies, 12 the effect of HO-1 silencing has been evaluated in MeOV-1, MeTA and MeMI cells exposed to PLX4032. We proved that HO-1 silencing efficiently prevented the upregulation of HO-1 induced by 10 μM PLX4032 in MeOV-1 and MeTA and by 1 μM PLX4032 in MeMI, as shown by protein ( Fig.…”

“…4 Heme oxygenase 1 (HO-1) is an inducible enzyme able to provide a strong cytoprotective response against a wide range of stressors, such as oxidative stress, radiations, heavy metals and inflammatory cytokines. 11,12 Moreover, the involvement of HO-1 upregulation in the reduction of T eff lymphocyte recruitment in colorectal cancers has been demonstrated 13 and more recently, its role in breast cancer and melanoma immune-escape has been highlighted. The latter is generally quenched by ferritin or transported by membrane Fe-ATPases, in order to prevent its accumulation.…”

“…[8][9][10] Interestingly, it has been proved that the upregulation of HO-1 in cancer cells impairs tumor immune recognition decreasing cell-mediated toxicity. 11,12 Moreover, the involvement of HO-1 upregulation in the reduction of T eff lymphocyte recruitment in colorectal cancers has been demonstrated 13 and more recently, its role in breast cancer and melanoma immune-escape has been highlighted. 14 Natural killer (NK) cells are lymphocytes of the innate immune system that play a fundamental role in antitumor responses.…”

Increasing Heme Oxygenase-1-Expressing Macrophages Indicates a Tendency of Poor Prognosis in Advanced Colorectal Cancer

“…However, in many cancer tissues, HO-1 is induced, synthesized, and expressed as a result of various stresses such as hypoxia [16], and its expression is higher than in surrounding normal tissues [17,18]. Elevated expression of HO-1 is found in various cancer types and is associated with poor prognosis [19,20]. The effects of HO-1 in cancer are different from those in normal tissues, including immunosuppressive action [21], anti-inflammatory responses [10,22], angiogenic effects [11,18], and resistance to treatment with anticancer agents [23,24].…”