Therapeutic potential of the human endogenous retroviral envelope protein HEMO: a pan‐cancer analysis. Issue 7 (11th October 2021)

• Record Type: Journal Article
• Authors: Kasperek, Amélie; Béguin, Anthony; Bawa, Olivia; De Azevedo, Kévin; Job, Bastien; Massard, Christophe; Scoazec, Jean‐Yves; Heidmann, Thierry; Heidmann, Odile
• Is Part Of: Molecular oncology. Volume 16:Issue 7(2022)
• Page Start: 1451
• Page End: 1473
• Publication Date: 2021-10-11
• Subjects: cancer -- ERVMER34‐1 -- HEMO -- HERV -- TCGA -- Wnt/β‐catenin; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.13069
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : Human endogenous retroviruses represent approximately 8% of our genome. Most of these sequences are defective except for a few genes such as the ancestral retroviral HEMO envelope gene (Human Endogenous MER34 ORF), recently characterized by our group. In this study, we characterized transcriptional activation of HEMO in primary tumors from The Cancer Genome Atlas (TCGA) and in metastatic tumors from a Gustave Roussy cohort. Pan‐cancer detection of the HEMO protein in a series of patient samples validated these results. Differential gene expression analysis in various TCGA datasets revealed a link between HEMO expression and activation of Wnt/β‐catenin signaling, in particular in endometrial cancer. Studies on cell models led us to propose that the Wnt/β‐catenin pathway could act as an upstream regulator of this retroviral endogenous sequence in tumor condition. Characterization of transcriptomic profiles of both HEMO Low and HEMO High tumors suggested that activation of HEMO is negatively associated with immune response signatures. Taken together, these results highlight that HEMO, as an endogenous retroviral envelope protein specifically expressed in tumors, represents a promising tumor biomarker and therapeutic target. Abstract : Human endogenous retroviruses represent approximately 8% of our genome. Among these sequences, HEMO (Human Endogenous MER34 ORF) is the oldest retroviral envelope gene, endogenized 100 million years ago. Using in silico and experimental pan‐cancer approaches, we showed that the HEMO protein is a tumor biomarker whose expression can be regulated by the Wnt/β‐catenin pathway.