Cancer-associated fibroblast-derived CCL5 enhanced aerobic glycolysis through upregulation of IP3R to promote breast cancer cell metastasis.

BACKGROUND

This study aimed to investigate whether cancer-associated fibroblast (CAF)-derived chemokine C-C motif ligand 5 (CCL5) promotes breast cancer (BC) cell metastasis by enhancing aerobic glycolysis via upregulation of IP3R.

METHODS

Lentiviral vectors for CCL5 overexpression or knockdown were constructed, transfected into CAFs, and co-cultured with ZR-75-30 cells CCL5. Cell proliferation and apoptosis were assessed by CCK-8, cloning assay and flow cytometry. Cell migration and invasion were verified by scratch assay and Transwell assay. Co-IP verified the interactions between CCL5 and IP3R. The kit detects aerobic glycolysis-related indexes. western bloting detects CCL5, IP3R, glycolysis-related proteins, EMT-related proteins and metastasis-related proteins.

RESULTS

Knockdown of CCL5 in CAFs and co-culture with breast cancer cells resulted in decreased cell proliferation, migration, and invasionCCL5, increased apoptosis, and attenuated aerobic glycolysis. Co-immunoprecipitation (Co-IP) assays revealed direct protein-protein interactions between CCL5 and IP3RCCL5. IP3R overexpression following CCL5 knockdown rescued breast cancer cell proliferative viability CCL5, restoration of migration and invasion abilities, and enhanced aerobic glycolysis.

CONCLUSION

CAF-derived CCL5 enhanced aerobic glycolysis in breast cancer cells by up-regulating IP3R expression, which in turn promoted their metastasis.

DATA AVAILABILITY: The data used to support the findings of this study are available from the corresponding author upon request.