Platelet isoform of phosphofructokinase accelerates malignant features in breast cancer
Takahiro Inaishi, Masahiro Shibata, Takahiro Ichikawa, Mitsuro Kanda, Masamichi Hayashi, Ikumi Soeda, Dai Takeuchi, Yuko Takano, Nobuyuki Tsunoda, Yasuhiro Kodera, Toyone Kikumori
Abstract
The platelet isoform of phosphofructokinase (PFKP) is one of the key enzymes in the glycolytic pathway. <em>PFKP</em> 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. The present study aimed to evaluate the function of PFKP in BC cells and its expression level in patients with BC. Firstly, 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 <em>PFKP</em> and 84 cancer‑related genes. Then, <em>PFKP</em> knockdown was conducted using small interfering RNA, and cell proliferation, invasiveness and migration were analyzed. Furthermore, the association between <em>PFKP</em> mRNA expression and clinicopathological factors was investigated in 167 patients with BC. <em>PFKP</em> was highly expressed in estrogen receptor‑negative and human epidermal growth factor receptor 2‑negative BC cell lines. PCR array analysis demonstrated that the expression level of <em>PFKP</em> was significantly correlated with that of transforming growth factor‑β1 and MYC proto‑oncogene. <em>PFKP</em> 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 exhibited higher expression of <em>PFKP</em> mRNA than patients with less severe disease. In conclusion, the present findings indicated that PFKP is involved in promoting tumor‑progressive oncological roles in BC cells across different subtypes and is considered a possible novel therapeutic target for BC.