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Journal of Cancer Prevention


J Cancer Prev 2022; 27(1): 7-15

Published online March 30, 2022

© Korean Society of Cancer Prevention

Non-canonical vs. Canonical Functions of Heme Oxygenase-1 in Cancer

Achanta Sri Venakata Jagadeesh1 , Xizhu Fang2 , Seong Hoon Kim2 , Yanymee N. Guillen-Quispe3 , Jie Zheng2 , Young-Joon Surh1,2 , Su-Jung Kim3

1Cancer Research Institute, Seoul National University, 2Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 3Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea

Correspondence to :
Su-Jung Kim, E-mail:,

Received: March 11, 2022; Revised: March 23, 2022; Accepted: March 23, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Heme oxygenase-1 (HO-1) is a critical stress-responsive enzyme that has antioxidant and anti-inflammatory functions. HO-1 catalyzes heme degradation, which gives rise to the formation of carbon monoxide (CO), biliverdin, and iron. The upregulation of HO-1 under pathological conditions associated with cellular stress represents an important cytoprotective defense mechanism by virtue of the anti-oxidant properties of the bilirubin and the anti-inflammatory effect of the CO produced. The same mechanism is hijacked by premalignant and cancerous cells. In recent years, however, there has been accumulating evidence supporting that the upregulation of HO-1 promotes cancer progression, independently of its catalytic activity. Such non-canonical functions of HO-1 are associated with its interaction with other proteins, particularly transcription factors. HO-1 also undergoes post-translational modifications that influence its stability, functional activity, cellular translocation, etc. HO-1 is normally present in the endoplasmic reticulum, but distinct subcellular localizations, especially in the nucleus, are observed in multiple cancers. The nuclear HO-1 modulates the activation of various transcription factors, which does not appear to be mediated by carbon monoxide and iron. This commentary summarizes the non-canonical functions of HO-1 in the context of cancer growth and progression and underlying regulatory mechanisms.

Keywords: Heme oxygenase-1, Cancer, Protein-protein interaction, Post-translational modification

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