CCL5 and GLUT1 define leader cells in collective invasion of colorectal cancer.

ABSTRACT: Invasion and metastasis in multiple solid tumors are promoted by collective invasion which is organized by leader and follower cells. Yet in colorectal cancer (CRC), biomarkers and mechanisms that specify leader cells remain undefined. Here we identify biomarkers of leader cells and elucidate how they drive CRC collective invasion and metastasis. Using a 3D photoconvertible CRC spheroid model, we isolated leader and follower cells. Transcriptomic, functional and in vivo assays show that GLUT1, PLOD2, and CCL5 in leader cells are indispensable for collective invasion. CCL5 activates PI3K/AKT signaling to up-regulate GLUT1 and PLOD2 in leader cells. Moreover, GLUT1 and CCL5 could serve as specific biomarkers for leader cells in CRC collective invasion, and their co-expression correlates with

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC13635607 | biostudies-literature | 2026 Aug

REPOSITORIES: biostudies-literature