STARD10 promotes progression of HER2+ breast cancer and intracellular lipid metabolism via the cAMP/PKA/CREB1 signaling axis.

BACKGROUND

Although targeted therapies have improved clinical outcomes, HER2+ breast cancer remains a significant clinical challenge due to its aggressive behavior and unfavorable prognosis. Emerging evidence indicates that dysregulated lipid metabolism plays a critical role in tumorigenesis and metastasis, suggesting that targeting lipid metabolism may represent a promising therapeutic strategy. STARD10, a lipid transport protein, plays a pivotal role in regulating lipid metabolism. However, its function in mediating lipid metabolism and tumor progression in HER2+ breast cancer remains unclear.

METHODS

The expression level and prognostic relevance of STARD10 in HER2+ breast cancer were analyzed using public databases and clinical cohorts. CCK-8, EdU, colony formation, transwell, LD540, and Nile Red staining assays were performed in SKBR3 and HCC1954 cells. Subcutaneous implantation and tail vein injection were performed to evaluate the effects of STARD10 overexpression on tumor growth and lung metastasis in vivo. The mechanism was validated by RNA-seq and Western blotting.

RESULTS

STARD10 expression was upregulated in HER2+ breast cancer tissues and was significantly correlated with poor prognosis. Functionally, STARD10 overexpression enhanced HER2+ breast cancer cell proliferation, migration, invasion, and lipid droplets accumulation. Moreover, STARD10 overexpression markedly accelerated tumor growth and lung metastasis in vivo. Mechanistically, STARD10 was found to drive malignant phenotypes via activation of the cAMP/PKA/CREB1 signaling axis.

CONCLUSION

STARD10 promotes malignant progression of HER2+ breast cancer and lipid droplets accumulation by activating the cAMP/PKA/CREB1 pathway. These findings suggest that STARD10 and the cAMP/PKA/CREB1 signaling axis as potential therapeutic targets for the treatment and prevention of HER2+ breast cancer.