Abstract A012: Role of STX1A in mediating Cathepsin G’s entry into human colorectal cancer cells

Abstract

Neutrophils with anti-tumor potential have the capability to kill cancer cells in a contact-dependent manner. It has been reported that Cathepsin G (CG), a serine protease mainly expressed in neutrophils, aids in the targeting of cancer cells. Nevertheless, the molecular mechanisms underlying NETosis released CG remain unexplored. This study aims to focus attention on the prospective mechanisms that could offer soluble CG the potential to kill cancer cells. Our previous CRISPR knockout (KO) screen targeting membrane trafficking found that several KO genes, including STX1A, suppress CG’s induced apoptosis in cancer cells, indicating its role in assisting CG cell entry. Based on the results, special attention was directed towards STX1A and its effect on CG’s role in anti-cancer activity. This project aims to address the molecular mechanisms underlying CG induced apoptosis in cancer cells. Via a better understanding of the mediators that promote CG entry into cells, we intent to call attention to beneficial effects modulated by CG in the tumorigenic environment. STX1A KO HCT116 cells were generated via the use of a lentivrus, and protein levels in these cells as well as in wild type HCT116 were determined. Immunofluorescence (IF) was utilized to visualize the localization of CG in both cell types. Our preliminary results show decreased CG signals in HCT116 STX1A KO cells treated with CG compared to control, calling attention to a likely role mediated by STX1A involving CG’s entry into cancer cells. Confirming our hypothesis can have beneficial implications in innovative  therapeutic approaches targeting colorectal carcinoma and possibly other types of cancer.

Citation Format: Valery Rozen, Yuxiang Wang, Zhenghe Wang. Role of STX1A in mediating Cathepsin G’s entry into human colorectal cancer cells [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A012.