Role and mechanism of sarcosine dehydrogenase in the progression of gallbladder cancer through chemokine pathways.

Background: Sarcosine dehydrogenase (SARDH) and C-X-C motif chemokine ligand 1 (CXCL1) have been identified as potential tumor regulators, with growing evidence linking them to cancer progression. However, their specific roles, regulatory mechanisms, and influence on key signaling pathways remain unclear.

Aim: To investigate the regulatory mechanisms of SARDH and CXCL1 in cancer cells and their impact on key signaling pathways.

Methods: Real-time quantitative polymerase chain reaction and western blot analyses were used to assess the expression levels of SARDH and CXCL1 and their effects on protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) signaling pathways. Gene overexpression was induced using an expression vector, while gene silencing was achieved using short hairpin RNA and small interfering RNA. CCK-8, migration, and invasion assays were used to evaluate the impact of gene suppression and overexpression on cancer cell proliferation, migration, and invasion.

Results: SARDH silencing significantly enhanced cancer cell proliferation, whereas its overexpression suppressed proliferation in the early stages of the experiment. CXCL1 silencing reduced cancer cell migration and invasion. SARDH overexpression inhibited cell migration, invasion, and adhesion while increasing apoptosis. Conversely, SARDH silencing reversed these effects. Furthermore, simultaneous silencing of SARDH and CXCL1 strongly activated the Akt and ERK signaling pathways, indicating the potential role of these pathways in regulating cellular functions influenced by these genes.

Conclusion: This study revealed that SARDH and CXCL1 regulate cancer cell growth, migration, and invasion through Akt and ERK signaling pathways, highlighting their potential as therapeutic targets for cancer treatment.