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Discovering the causes of cancer and the means of prevention

The long and the short of the SARS-CoV-2 receptor ACE2 and what this means for all of us - Dr. Prokunina-Olsson

DCEG Seminar

October 1, 2020 | 10:30 AM – 11:30 AM

Online via Webex

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Ludmila Prokunina-Olsson, Ph.D.
Chief and senior investigator,
Laboratory of Translational Genomics
Division of Cancer Epidemiology & Genetics


Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes COVID-19, utilizes angiotensin-converting enzyme 2 (ACE2) for entry into target cells. ACE2 has been proposed as an interferon-stimulated gene (ISG). Thus, interferon-induced variability in ACE2 expression levels could be important for susceptibility to COVID-19 or its outcomes. We discovered a novel, transcriptionally-independent truncated isoform of ACE2, which we designate as deltaACE2 (dACE2). By cloning and functional annotation, we demonstrate that dACE2, but not ACE2, is an ISG. In The Cancer Genome Atlas (TCGA), the expression of dACE2 was enriched in squamous tumors of the respiratory, gastrointestinal, and urogenital tracts. In vitro, dACE2, which lacks 356 N-terminal amino acids, was non-functional in binding the SARS-CoV-2 spike protein and as a carboxypeptidase. Our results suggest that the ISG-type induction of dACE2 in IFN-high conditions created by treatments, inflammatory tumor microenvironment, or viral co-infections is unlikely to increase the cellular entry of SARS-CoV-2 and promote infection. The role of ACE2 and dACE2 in cancer patients needs to be further explored and considered in COVID-19 outcomes.

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