Journal
AMERICAN JOURNAL OF CANCER RESEARCH
Volume 11, Issue 10, Pages 4994-5005Publisher
E-CENTURY PUBLISHING CORP
Keywords
SARS-CoV-2 variant; glycosylation; epithelial-mesenchymal transition; spike; NF-kappa B
Categories
Funding
- Ministry of Science and Technology [MOST 109-2314-B-001-002, MOST 109-2314-B-001-008, MOST-108-3114-Y-001-002, MOST 108-2320-B-001-034-MY2, MOST 109-3114-Y-001-001]
- Academia Sinica [AS-SUMMIT-109, AS-KPQ-109-BioMed, AS-CDA-110-L09, AS-GC-110-05, AS-KPQ-110-EIMD]
- University of Massachusetts Lowell [D502-10000000022]
- Taiwan CDC [AS-CFII-108-102]
- DNA Sequencing Core Facility [AS-CFII-108-115]
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An investigation found that the Gamma variant of SARS-CoV-2 activates NF-kappa B signaling, leading to pro-survival functions in cancer progression. Inhibiting NF-kappa B could reduce the risk of chronic diseases in COVID-19 patients.
SARS-CoV-2 exploits the host cellular machinery for virus replication leading to the acute syndrome of coronavirus disease 2019 (COVID-19). Growing evidence suggests SARS-CoV-2 also exacerbates many chronic diseases, including cancers. As mutations on the spike protein (S) emerged as dominant variants that reduce vaccine efficacy, little is known about the relation between SARS-CoV-2 virus variants and cancers. Compared to the SARS-CoV-2 wild-type, the Gamma variant contains two additional NXT/S glycosylation motifs on the S protein. The hyperglycosylated S of Gamma variant is more stable, resulting in more significant epithelial-mesenchymal transition (EMT) potential. SARS-CoV-2 infection promoted NF-kappa B signaling activation and p65 nuclear translocation, inducing Snail expression. Pharmacologic inhibition of NF-kappa B activity by nature food compound, 13C suppressed viral replication and Gamma variant-mediated breast cancer metastasis, indicating that NF-kappa B inhibition can reduce chronic disease in COVID-19 patients. Our study revealed that the Gamma variant of SARS-CoV-2 activates NF-kappa B and, in turn, triggers the pro-survival function for cancer progression.
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