Epithelial-mesenchymal transition induced by SARS-CoV-2 required transcriptional upregulation of Snail

Yun-Ju Lai; Chi-Hong Chao; Chun-Che Liao; Te-An Lee; Jung-Mao Hsu; Wen-Cheng Chou; Jyun Wang; Hsiang-Chi Huang; Shing-Jyh Chang; Yi-Ling Lin; Chia-Wei Li

Epithelial-mesenchymal transition induced by SARS-CoV-2 required transcriptional upregulation of Snail

Am J Cancer Res. 2021 May 15;11(5):2278-2290. eCollection 2021.

Authors

Yun-Ju Lai^{1

2}, Chi-Hong Chao^{3

4

5}, Chun-Che Liao¹, Te-An Lee¹, Jung-Mao Hsu⁶, Wen-Cheng Chou¹, Jyun Wang¹, Hsiang-Chi Huang¹, Shing-Jyh Chang⁷, Yi-Ling Lin^{1

8}, Chia-Wei Li¹

Affiliations

¹ Institute of Biomedical Sciences, Academia Sinica Taipei 115, Taiwan.
² Solomont School of Nursing, Zuckerberg College of Health Sciences, University of Massachusetts Lowell 113 Wilder Street, Lowell, MA 01854, USA.
³ Department of Biological Science and Technology, National Chiao Tung University Hsinchu 30010, Taiwan.
⁴ Department of Biological Science and Technology, National Yang Ming Chiao Tung University Hsinchu 30010, Taiwan.
⁵ Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Chiao Tung University Hsinchu 30010, Taiwan.
⁶ Graduate Institute of Biomedical Sciences and Research Center for Cancer Biology, Medical University Taichung 406040, Taiwan.
⁷ Department of Obstetrics and Gynecology, Hsinchu MacKay Memorial Hospital Hsinchu 300, Taiwan.
⁸ Biomedical Translational Research Center, Academia Sinica Taipei 115, Taiwan.

PMID: 34094684
PMCID: PMC8167694

Abstract

The engagement of human angiotensin-converting enzyme 2 (hACE2) and SARS-CoV-2 spike protein facilitate virus spread. Thus far, ACE2 and TMPRSS2 expression is correlated with the epithelial-mesenchymal transition (EMT) gene signature in lung cancer. However, the mechanism for SARS-CoV-2-induced EMT has not been thoroughly explored. Here, we showed that SARS-CoV-2 induces EMT phenotypic change and stemness in breast cancer cell model and subsequently identified Snail as a modulator for this regulation. The in-depth analysis identifies the spike protein (S), but not envelope (E), nucleocapsid (N), or membrane protein (M), of SARS-CoV-2 induces EMT marker changes. Suppression of Snail expression in these cells abrogates S protein-induced invasion, migration, stemness, and lung metastasis, suggesting that Snail is required for SARS-CoV-2-mediated aggressive phenotype in cancer. This study reveals an important oncogenic role of SARS-CoV-2 in triggering breast cancer metastasis through Snail upregulation.

Keywords: ACE2; EMT; SARS-CoV-2; Snail; TMPRSS2; epithelial-mesenchymal transition; spike.