Research Stories
The SARS-CoV-2 spike protein induces lung cancer migration and invasion in a TLR2-dependent manner
lung cancer genetic data are being used to identify novel factors capable of regulating cancer development and progression, providing therapeutic strategy for the intervention of lung cancers
Medicine
Prof.
LEE, KI YOUNG
Dr. Mi-Jeong Kim
It has been reported that lung cancer development and progression are induced by genetic mutations and various external factors. Recently, lung cancer genetic data are being used to identify novel factors capable of regulating cancer development and progression, thereby providing therapeutic strategy for the intervention of lung cancers.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to severe outcomes in patients with cancer. It has been reported that patients with lung cancers disproportionately manifest severe COVID-19 with a high rate of hospitalization and death. Notably, the SARS-CoV-2 Spike (S) protein can induce hyper-inflammation in both epithelial cells and macrophages through toll-like receptor (TLR)1/TLR2 or TLR2/6-dependent nuclear factor-kappaB (NF-κB) pathway. However, molecular and cellular evidence on whether the SARS-CoV-2 virus affects the severity of lung cancer patients through TLR1/2 or TLR2/6 signaling remains unclear.
In this study, we provide evidence about how SARS-CoV-2 critically affects viral susceptibility and severity in patients with lung cancer. Our data demonstrate that lung cancer patients with up-regulated ACE2, TMPRSS2, TLR1, TLR2, and TLR6 are more likely to be susceptible to SARS-CoV-2 infection than those with down-regulated ACE2, TMPRSS2, TLR1, TLR2, and TLR6, subsequently leading to a more severe SARS-CoV-2 infection followed by promoting cancer progression through TLR2-dependent activation of NF-κB. However, it is still controversial of the role of TLR2 in lung tumor progression because TLR2 orchestrates a tumor suppressor response in early-stage lung cancer through the induction of cell-autonomous and non-cell-autonomous tumor suppressor responses. Although the precise molecular and cellular mechanisms by which TLR2 is functionally implicated in different stages of lung cancer is absolutely required, the current study gives insight into cellular and molecular mechanisms by which SARS-CoV-2 infection influences lung cancer progression in a TLR2-dependent manner. It might contribute to our understanding of the susceptibility to and the severity of SARS-CoV-2 infection in patients with lung cancer.
* The results of this research were published in Cancer communications (IF=16.2), a world-class oncology journal, on 2023 Sep 13. This study was performed by Dr. Mi-Jeong Kim (BK21 FOUR in Sungkyunkwan University School of Medicine), Ji Young Kim (a Ph.D. student in Sungkyunkwan University School of Medicine) and Ji Hye Shin (a Ph.D. student in Sungkyunkwan University School of Medicine) as the co-first author. This work was supported by the National Research Foundation of Korea Grants funded by the Korean Government (2023R1A2C1003762 and RS-2023-00217189).
FIGURE 1: SARS-CoV-2 spike protein induces lung cancer migration and invasion in a TLR2-dependent manner.
