Dysregulated ceramides metabolism via PTPN11 exposes a metabolic vulnerability to breast cancer metastasis.

Abstract

Breast cancer is a prevalent malignant tumor, posing a significant threat to women's health globally due to its increasing incidence and tendency to affect younger patients. Protein tyrosine phosphatases (PTPs) are a class of enzymes that have emerged as potential targets for various tumors, including breast cancer, because they can modulate oncogenic tyrosine kinases, which are both tumor-suppressive and oncogenic. The regulation of tyrosine phosphorylation levels is crucial for cell proliferation and differentiation. Although the clinical biomarker potential of PTPs is not fully explored, there is evidence to suggest that they may serve as clinical biomarkers and therapeutic targets for breast cancer. We found that increased expression levels of PTPN11 and PTPN3 were associated with a higher risk of death in patients with breast cancer, while PTPN11 and PTPN18 are significantly associated with overall survival in patients with estrogen receptor-positive (ER+) breast cancer. Meanwhile, PTPN11 expression was found to be negatively associated with survival in patients with ER+ breast cancer. Furthermore, PTPN11 exposes a metabolic vulnerability to breast cancer metastasis via dysregulated ceramide metabolism. Therefore, we speculate that PTPN11 has the potential to serve as a therapeutic target for breast cancer by regulating lipid metabolism reprogramming.