Single cell analysis of mechanical properties and EMT-related gene expression profiles in cancer fingers

Heng Zou; Zihan Yang; Yuen-San Chan; Sung-King Au Yeung; Md Kowsar Alam; Tongxu Si; Tao Xu; Mengsu Yang

doi:10.1016/j.isci.2022.103917

Single cell analysis of mechanical properties and EMT-related gene expression profiles in cancer fingers

iScience. 2022 Feb 12;25(3):103917. doi: 10.1016/j.isci.2022.103917. eCollection 2022 Mar 18.

Authors

Heng Zou^{1

2}, Zihan Yang^{1

3}, Yuen-San Chan^{1

2}, Sung-King Au Yeung^{1

3}, Md Kowsar Alam^{1

4}, Tongxu Si^{1

3}, Tao Xu^{1

2}, Mengsu Yang^{1

3

2}

Affiliations

¹ Department of Biomedical Sciences, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, People's Republic of China.
² Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institutes of City University of Hong Kong, Shenzhen, People's Republic of China.
³ Tung Biomedical Sciences Centre, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, People's Republic of China.
⁴ Department of Physics, University of Chittagong, Chittagong, Bangladesh.

Abstract

Collective cell migration is associated with cancer metastasis. Cancer fingers are formed when groups of migrating cancer cells follow the leader cells in the front. Epithelial to mesenchymal transition (EMT) is a critical process of cancer metastasis. However, the role of EMT in cancer finger formation remains unclear. In this work, we investigated the EMT-associated mechanical properties and gene expression at single-cell levels in non-small lung cancer fingers. We found that leader cells were more elastic and less sticky than follower cells. Spatial EMT-related gene expression profiling in cancer fingers revealed cellular heterogeneity. Particularly, SNAIL and VIM were found to be two key genes that positively correlated with leader cell phenotypes and controlled cancer finger formation. Silencing either SNAIL or VIM, decreased cancer cell elasticity, cancer finger formation and migration, and increased adhesiveness. These findings indicated that SNAIL and VIM are two driver genes for cancer finger formation.

Keywords: Cancer; Cell biology; Transcriptomics.