Abstract
Background
Cancer cells depend on a plentiful glucose supply to sustain rapid proliferation. When glucose becomes limited, they undergo adaptive changes to survive and metastasize, yet the underlying molecular mechanisms remain poorly defined.
Methods
LRRC15 expression was assessed in breast cancer cells under varying glucose concentrations. Its biological role was explored through RNA interference and neutralizing antibody experiments in vitro, as well as in mouse xenograft and metastasis models.
Results
Low glucose (1.0 g/L) strongly induced LRRC15 expression in a manner involving the transcription factor C/EBPα, an effect reversed by restoring high glucose (4.5 g/L). Depletion of LRRC15 inhibited cell growth and migration and attenuated the enhanced migration induced by low glucose. In vivo, LRRC15 knockdown reduced tumor burden and distant metastases, and a monoclonal antibody targeting LRRC15 significantly inhibited orthotopic tumor growth and metastasis.
Conclusion
These findings establish LRRC15 as a glucose-responsive gene that drives breast cancer cell growth and metastasis, underscoring its promise as a therapeutic target for metastatic breast cancer.