Lai Yun-Ju, Chao Chi-Hong, Liao Chun-Che, Lee Te-An, Hsu Jung-Mao, Chou Wen-Cheng, Wang Jyun, Huang Hsiang-Chi, Chang Shing-Jyh, Lin Yi-Ling, Li Chia-Wei
Institute of Biomedical Sciences, Academia Sinica Taipei 115, Taiwan.
Solomont School of Nursing, Zuckerberg College of Health Sciences, University of Massachusetts Lowell 113 Wilder Street, Lowell, MA 01854, USA.
Am J Cancer Res. 2021 May 15;11(5):2278-2290. eCollection 2021.
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.
人血管紧张素转换酶2（hACE2）与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白的结合促进了病毒传播。到目前为止，ACE2和跨膜丝氨酸蛋白酶2（TMPRSS2）的表达与肺癌中的上皮-间质转化（EMT）基因特征相关。然而，SARS-CoV-2诱导EMT的机制尚未得到充分探索。在此，我们表明SARS-CoV-2在乳腺癌细胞模型中诱导EMT表型变化和干性，随后鉴定出Snail是这种调节的调节因子。深入分析确定SARS-CoV-2的刺突蛋白（S）而非包膜蛋白（E）、核衣壳蛋白（N）或膜蛋白（M）诱导EMT标志物变化。抑制这些细胞中Snail的表达可消除S蛋白诱导的侵袭、迁移、干性和肺转移，这表明Snail是SARS-CoV-2介导的癌症侵袭性表型所必需的。这项研究揭示了SARS-CoV-2通过上调Snail触发乳腺癌转移的重要致癌作用。
