PFKP Accelerates Malignant Features in Breast Cancer

Abstract Purpose The platelet isoform of phosphofructokinase (PFKP) is one of the key enzymes in the glycolytic pathway. PFKP is highly expressed in several cancers, and it has been reported to be involved in the progression of cancer cells. However, its oncological role in breast cancer (BC) remains unclear. This study aimed to evaluate the function of PFKP in BC cells and its expression level in patients with BC.Methods The mRNA and protein expression of PFKP was evaluated in BC and non-cancerous mammary cell lines. Polymerase chain reaction (PCR) array analysis was conducted to evaluate the correlation between PFKP and 84 cancer-related genes. PFKP knockdown was conducted using small interfering RNA, and cell proliferation, invasiveness, and migration were analyzed. Furthermore, the association between PFKP mRNA expression and clinicopathological factors was investigated in 167 patients with BC.Results PFKP was highly expressed in estrogen receptor-negative and human epidermal growth factor receptor 2-negative BC cell lines. PCR array analysis demonstrated that PFKP expression level significantly correlated with that of transforming growth factor beta 1 and MYC proto-oncogene. PFKP knockdown significantly decreased the proliferation and invasiveness of MCF7, SK-BR-3, and MDA-MB-231 cells. Furthermore, cell migration was inhibited in SK-BR-3 and MDA-MB-231 cells. In the clinical specimens, patients with T2/T3/T4, lymph node metastasis, or stage II/III/IV showed higher expression of PFKP mRNA than patients with less severe disease.Conclusions PFKP is involved in promoting tumor-progressive oncological roles in BC cells across different subtypes. PFKP is considered a possible novel therapeutic target for BC.