Platelet isoform of phosphofructokinase accelerates malignant features in breast cancer

Abstract

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. 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 PFKP and 84 cancer-related genes. Then, 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. PFKP 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 PFKP was significantly correlated with that of transforming growth factor-β1 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 exhibited higher expression of PFKP 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.

Biomimetic Synthesis and Chemical Proteomics Reveal the Mechanism of Action and Functional Targets of Phloroglucinol Meroterpenoids

“…Consequently, we next aimed to assess the functional impact of representative lysine–meroterpenoid interactions on target proteins. Proteins crucial to metabolic pathways that are essential for breast cancer progressionnamely, lipid metabolism (ABHD12), mitochondrial respiration (IDH2), and glycolysis (PFKP, PFKM, PFKL), , were chosen not only for their individual roles but also for their interplay with the mechanisms that regulate mitochondrial dynamics.…”

Phosphofructokinase Platelet Overexpression Accelerated Colorectal Cancer Cell Growth and Motility

“…Wang et al reported that PFKP overexpression inhibited cancer cell apoptosis and accelerated the growth, migration, and invasion of H1299 cells [33]. In breast cancer, PFKP expression was negatively correlated with estrogen receptor and human epidermal growth factor receptor-2 and positively correlated with transforming growth factor-β and MYC expression [34]. A study reported that PFKP expression was positively associated with estrogen receptor-and progesterone receptor-negative breast cancers [29].…”

“…A study reported that PFKP expression was positively associated with estrogen receptor-and progesterone receptor-negative breast cancers [29]. Decreased PFKP expression significantly suppressed breast cancer cell growth and invasion [34]. A dietary polyphenolic compound, quercetin, suppressed growth and migration by inhibiting PFKP and LDHA expression in breast cancer [29].…”

Energy metabolism pathways in breast cancer progression: The reprogramming, crosstalk, and potential therapeutic targets

“…PFKP is gaining attention for its significant role in BC progression. Highly expression of PFKP was observed in estrogen receptor‑negative and human epidermal growth factor receptor (EGFR) 2‑negative BC cell lines [26] and human BC tissues [25] . The knockdown of PFKP significantly attenuated the proliferation and invasiveness in MCF7, SK‑BR‑3, and MDA‑MB‑231 BC cells [26] , and the role of PFKP in promoting tumor progressive oncology was speculated to be clearly related to transforming growth factor‑β1 and MYC proto‑oncogene [26] .…”

“…Highly expression of PFKP was observed in estrogen receptor‑negative and human epidermal growth factor receptor (EGFR) 2‑negative BC cell lines [26] and human BC tissues [25] . The knockdown of PFKP significantly attenuated the proliferation and invasiveness in MCF7, SK‑BR‑3, and MDA‑MB‑231 BC cells [26] , and the role of PFKP in promoting tumor progressive oncology was speculated to be clearly related to transforming growth factor‑β1 and MYC proto‑oncogene [26] . Not only the foregoing, but the high expression of PFKP associated with the increased PFKP S386 phosphorylation was identified in Wnt signaling‑induced BC development in a β‑catenin‑independent manner [27] or the activation of Kru¨ppel-like factor in BC cells [28] .…”