Heme Oxygenase-1 and Its Role in Colorectal Cancer

Heme oxygenase-1 (HO-1) is an enzyme located at the endoplasmic reticulum, which is responsible for the degradation of cellular heme into ferrous iron, carbon monoxide and biliverdin-IXa. In addition to this main function, the enzyme is involved in many other homeostatic, toxic and cancer-related mechanisms. In this review, we first summarize the importance of HO-1 in physiology and pathophysiology with a focus on the digestive system. We then detail its structure and function, followed by a section on the regulatory mechanisms that control HO-1 expression and activity. Moreover, HO-2 as important further HO isoform is discussed, highlighting the similarities and differences with regard to HO-1. Subsequently, we describe the direct and indirect cytoprotective functions of HO-1 and its breakdown products carbon monoxide and biliverdin-IXa, but also highlight possible pro-inflammatory effects. Finally, we address the role of HO-1 in cancer with a particular focus on colorectal cancer. Here, relevant pathways and mechanisms are presented, through which HO-1 impacts tumor induction and tumor progression. These include oxidative stress and DNA damage, ferroptosis, cell cycle progression and apoptosis as well as migration, proliferation, and epithelial-mesenchymal transition.

Automated summary

This review highlights the importance of heme oxygenase-1 (HO-1) in the physiology and pathophysiology of the digestive system. It provides an overview of the structure, function, and regulatory mechanisms of HO-1, as well as discussing the similarities and differences with HO-2. The review also explores the cytoprotective and potential pro-inflammatory effects of HO-1 and its breakdown products. Furthermore, it discusses the role of HO-1 in colorectal cancer, focusing on pathways and mechanisms involved in tumor induction and progression.