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Investigating TNS4 in the Colorectal Tumor Microenvironment Using 3D Spheroid Models of Invasion

Raposo, Teresa P.; Susanti, Susanti; Ilyas, Mohammad

Investigating TNS4 in the Colorectal Tumor Microenvironment Using 3D Spheroid Models of Invasion Thumbnail


Authors

Teresa P. Raposo

Susanti Susanti



Abstract

TNS4 (Tensin 4 or Cten) is a putative oncogene in colorectal cancer (CRC) with a role in regulating cell adhesion, motility, invasion, and epithelial to mesenchymal transition (EMT). The objective is to study the role of TNS4 in CRC using more realistic models of the tumor microenvironment. CRC cells expressing TdTomato protein and shTNS4/shLUC hairpin oligos are grown in 3D spheroids with and without cancer?associated fibroblasts (CAFs). Adhesiveness to collagen I and CAFs is assessed in 2D and cell proliferation, volume, and invasion are assessed in 3D conditions. The role of TNS4 knockdown in gefitinib chemosensitivity and epidermal growth factor receptor (EGFR) and Ras protein levels are also tested. In general, TNS4 knockdown increases cell proliferation in cell lines producing compact spheroids. The addition of CAFs in spheroids supports CRC cell proliferation, whereas CAFs themselves do not proliferate, but increases ECM degradation. TNS4 knockdown reduces adhesiveness and 3D invasion and disrupts EGFR signaling which results in increased sensitivity to Gefitinib. In conclusion, in a 3D spheroid model, TNS4 inhibits cell proliferation and promotes cell invasion into the ECM, possibly by adhesion to the ECM and stromal cells. TNS4 knockdown enhances sensitivity to the EGFR inhibitor gefitinib and may be helpful for Kirsten ras oncogene homolog mutant CRC patients.

Citation

Raposo, T. P., Susanti, S., & Ilyas, M. (2020). Investigating TNS4 in the Colorectal Tumor Microenvironment Using 3D Spheroid Models of Invasion. Advanced Biosystems, 4(6), https://doi.org/10.1002/adbi.202000031

Journal Article Type Article
Acceptance Date Apr 15, 2020
Online Publication Date May 10, 2020
Publication Date 2020-06
Deposit Date Nov 30, 2020
Publicly Available Date Mar 29, 2024
Journal Advanced Biosystems
Print ISSN 2366-7478
Electronic ISSN 2366-7478
Peer Reviewed Peer Reviewed
Volume 4
Issue 6
Article Number 2000031
DOI https://doi.org/10.1002/adbi.202000031
Public URL https://nottingham-repository.worktribe.com/output/5092248
Publisher URL https://onlinelibrary.wiley.com/doi/full/10.1002/adbi.202000031

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