ArticleOncogene2015
Signal peptide peptidase-mediated nuclear localization of heme oxygenase-1 promotes cancer cell proliferation and invasion independent of its enzymatic activity.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 51 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed, 89 citations in OpenAlex.
- Bottom-Up Model Suggesting Membrane Localization of Heme Oxygenase‑1 Contributes to Heme Selection for Degradation.ACS omega · 2026Article
- HMOX1 controls a heme-ferritin switch that protects cells from ferroptosis.Science advances · 2026Article
- Signal peptide peptidase- and SPP-like 3-dependent shedding of α1,6-fucosyltransferase differentially affects core fucosylation.The Journal of biological chemistry · 2026Article
- DLX4 regulates rheumatoid arthritis fibroblast-like synoviocytes invasiveness and a cancer transcriptomic signature.Scientific reports · 2025Article
- Low-Dose Quercetin Dephosphorylates AKT and Suppresses Proteins Related to Migration in Human Metastatic Uveal Melanoma Cells.Life (Basel, Switzerland) · 2025Article
- Article
- The DNase TREX1 is a substrate of the intramembrane protease SPP with implications for disease pathogenesis.Cellular and molecular life sciences : CMLS · 2025Article
- Targeting PTGDS Promotes ferroptosis in peripheral T cell lymphoma through regulating HMOX1-mediated iron metabolism.British journal of cancer · 2025Article
- HO-1 impairs the efficacy of radiotherapy by redistributing cGAS and STING in tumors.The Journal of clinical investigation · 2024Article
- Topology surveillance of the lanosterol demethylase CYP51A1 by signal peptide peptidase.Journal of cell science · 2024Article
- Review
- Proteomic analysis of the effect of hemin in breast cancer.Scientific reports · 2023Article
- Heme oxygenase 1 in erythropoiesis: an important regulator beyond catalyzing heme catabolism.Annals of hematology · 2023Review
- Hemoxygenase-1 Promotes Head and Neck Cancer Cell Viability.Antioxidants (Basel, Switzerland) · 2022Article
- Predictive and prognostic effect of HO-1 expression in breast cancer patients undergoing neoadjuvant chemotherapy.Breast cancer research and treatment · 2022Article
- Non-canonical vs. Canonical Functions of Heme Oxygenase-1 in Cancer.Journal of cancer prevention · 2022Review
- The Nuclear Translocation of Heme Oxygenase-1 in Human Diseases.Frontiers in cell and developmental biology · 2022Review
- The non-canonical effects of heme oxygenase-1, a classical fighter against oxidative stress.Redox biology · 2021Review
- Review
- An Analysis of the Multifaceted Roles of Heme in the Pathogenesis of Cancer and Related Diseases.Cancers · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heme oxygenase-1 (HO-1) is a heme-degrading enzyme anchored in the endoplasmic reticulum by a carboxyl-terminal transmembrane segment (TMS). HO-1 is highly expressed in various cancers and its nuclear localization is associated with the progression of some cancers. Nevertheless, the mechanism underlying HO-1 nuclear translocation and its pathological significance remain elusive. Here we show that the signal peptide peptidase (SPP) catalyzes the intramembrane cleavage of HO-1. Coexpression of HO-1 with wild-type SPP, but not a dominant-negative SPP, promoted the nuclear localization of HO-1 in cells. Mass spectrometry analysis of cytosolic HO-1 isolated from HeLa cells overexpressing HO-1 and SPP revealed two adjacent intramembrane cleavage sites located after S275 and F276 within the TMS. Mutations of S275F276 to A275L276 significantly hindered SPP-mediated HO-1 cleavage and nuclear localization. Nuclear HO-1 was detected in A549 and DU145 cancer cell lines expressing high levels of endogenous HO-1 and SPP. SPP knockdown or inhibition significantly reduced nuclear HO-1 localization in A549 and DU145 cells. The positive nuclear HO-1 stain was also evident in lung cancer tissues expressing high levels of HO-1 and SPP. Overexpression of a truncated HO-1 (t-HO-1) lacking the TMS in HeLa and H1299 cells promoted cell proliferation and migration/invasion. The effect of t-HO-1 was not affected by a mutation in the catalytic site. However, blockade of t-HO-1 nuclear localization abolished t-HO-1-mediated effect. The tumorigenic effect of t-HO-1 was also demonstrated in the mouse model. These findings disclose that SPP-mediated intramembrane cleavage of HO-1 promotes HO-1 nuclear localization and cancer progression independent of HO-1 enzymatic activity.
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