Bibliographic Details
| Title: |
Targeting the GPI transamidase subunit GPAA1 abrogates the CD24 immune checkpoint in ovarian cancer |
| Authors: |
Alok K. Mishra, Tianyi Ye, Shahid Banday, Ritesh P. Thakare, Chinh Tran-To Su, Ngoc N.H. Pham, Amjad Ali, Ankur Kulshreshtha, Shreya Roy Chowdhury, Tessa M. Simone, Kai Hu, Lihua Julie Zhu, Birgit Eisenhaber, Sara K. Deibler, Karl Simin, Paul R. Thompson, Michelle A. Kelliher, Frank Eisenhaber, Sunil K. Malonia, Michael R. Green |
| Source: |
Cell Reports, Vol 43, Iss 4, Pp 114041- (2024) |
| Publisher Information: |
Elsevier, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
CP: Cancer, Biology (General), QH301-705.5 |
| More Details: |
Summary: CD24 is frequently overexpressed in ovarian cancer and promotes immune evasion by interacting with its receptor Siglec10, present on tumor-associated macrophages, providing a “don’t eat me” signal that prevents targeting and phagocytosis by macrophages. Factors promoting CD24 expression could represent novel immunotherapeutic targets for ovarian cancer. Here, using a genome-wide CRISPR knockout screen, we identify GPAA1 (glycosylphosphatidylinositol anchor attachment 1), a factor that catalyzes the attachment of a glycosylphosphatidylinositol (GPI) lipid anchor to substrate proteins, as a positive regulator of CD24 cell surface expression. Genetic ablation of GPAA1 abolishes CD24 cell surface expression, enhances macrophage-mediated phagocytosis, and inhibits ovarian tumor growth in mice. GPAA1 shares structural similarities with aminopeptidases. Consequently, we show that bestatin, a clinically advanced aminopeptidase inhibitor, binds to GPAA1 and blocks GPI attachment, resulting in reduced CD24 cell surface expression, increased macrophage-mediated phagocytosis, and suppressed growth of ovarian tumors. Our study highlights the potential of targeting GPAA1 as an immunotherapeutic approach for CD24+ ovarian cancers. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2211-1247 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2211124724003693; https://doaj.org/toc/2211-1247 |
| DOI: |
10.1016/j.celrep.2024.114041 |
| Access URL: |
https://doaj.org/article/51c10ad4e53242b1b570a3e817e3e103 |
| Accession Number: |
edsdoj.51c10ad4e53242b1b570a3e817e3e103 |
| Database: |
Directory of Open Access Journals |
