tetano
Editor, Senior Moderator
Am J Cancer Res
. 2021 Oct 15;11(10):4994-5005.
eCollection 2021.
Hyperglycosylated spike of SARS-CoV-2 gamma variant induces breast cancer metastasis
Hsiang-Chi Huang[SUP] 1 [/SUP], Chun-Che Liao[SUP] 1 [/SUP], Shih-Han Wang[SUP] 1 [/SUP], I-Jung Lee[SUP] 1 [/SUP], Te-An Lee[SUP] 1 [/SUP], Jung-Mao Hsu[SUP] 2 [/SUP], Chun-Tse Kuo[SUP] 1 [/SUP], Jyun Wang[SUP] 1 [/SUP], Wan-Chen Hsieh[SUP] 1 [/SUP], Shing-Jyh Chang[SUP] 3 [/SUP], Shih-Yu Chen[SUP] 1 [/SUP], Mi-Hua Tao[SUP] 1 4 [/SUP], Yi-Ling Lin[SUP] 1 4 [/SUP], Yun-Ju Lai[SUP] 1 5 [/SUP], Chia-Wei Li[SUP] 1 [/SUP]
Affiliations
Abstract
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-κB signaling activation and p65 nuclear translocation, inducing Snail expression. Pharmacologic inhibition of NF-κB activity by nature food compound, I3C suppressed viral replication and Gamma variant-mediated breast cancer metastasis, indicating that NF-κB inhibition can reduce chronic disease in COVID-19 patients. Our study revealed that the Gamma variant of SARS-CoV-2 activates NF-κB and, in turn, triggers the pro-survival function for cancer progression.
Keywords: NF-κB; SARS-CoV-2 variant; epithelial-mesenchymal transition; glycosylation; spike.
. 2021 Oct 15;11(10):4994-5005.
eCollection 2021.
Hyperglycosylated spike of SARS-CoV-2 gamma variant induces breast cancer metastasis
Hsiang-Chi Huang[SUP] 1 [/SUP], Chun-Che Liao[SUP] 1 [/SUP], Shih-Han Wang[SUP] 1 [/SUP], I-Jung Lee[SUP] 1 [/SUP], Te-An Lee[SUP] 1 [/SUP], Jung-Mao Hsu[SUP] 2 [/SUP], Chun-Tse Kuo[SUP] 1 [/SUP], Jyun Wang[SUP] 1 [/SUP], Wan-Chen Hsieh[SUP] 1 [/SUP], Shing-Jyh Chang[SUP] 3 [/SUP], Shih-Yu Chen[SUP] 1 [/SUP], Mi-Hua Tao[SUP] 1 4 [/SUP], Yi-Ling Lin[SUP] 1 4 [/SUP], Yun-Ju Lai[SUP] 1 5 [/SUP], Chia-Wei Li[SUP] 1 [/SUP]
Affiliations
- PMID: 34765306
- PMCID: PMC8569360
Abstract
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-κB signaling activation and p65 nuclear translocation, inducing Snail expression. Pharmacologic inhibition of NF-κB activity by nature food compound, I3C suppressed viral replication and Gamma variant-mediated breast cancer metastasis, indicating that NF-κB inhibition can reduce chronic disease in COVID-19 patients. Our study revealed that the Gamma variant of SARS-CoV-2 activates NF-κB and, in turn, triggers the pro-survival function for cancer progression.
Keywords: NF-κB; SARS-CoV-2 variant; epithelial-mesenchymal transition; glycosylation; spike.