PPA1, an energy metabolism initiator, plays an important role in the progression of malignant tumors

Abstract

Inorganic pyrophosphatase (PPA1) encoded by PPA1 gene belongs to Soluble Pyrophosphatases (PPase) family and is expressed widely in various tissues of Homo sapiens, as well as significantly in a variety of malignancies. The hydrolysis of inorganic pyrophosphate (PPi) to produce orthophosphate (Pi) not only dissipates the negative effects of PPi accumulation, but the energy released by this process also serves as a substitute for ATP. PPA1 is highly expressed in a variety of tumors and is involved in proliferation, invasion, and metastasis during tumor development, through the JNK/p53, Wnt/β-catenin, and PI3K/AKT/GSK-3β signaling pathways. Because of its remarkable role in tumor development, PPA1 may serve as a biological target for adjuvant therapy of tumor malignancies. Further, PPA1 is a potential biomarker to predict survival in patients with cancer, where the assessment of its transcriptional regulation can provide an in-depth understanding. Herein, we describe the signaling pathways through which PPA1 regulates malignant tumor progression and provide new insights to establish PPA1 as a biomarker for tumor diagnosis.

Deregulated circRNAs in Epithelial Ovarian Cancer With Activity in PreclinicalIn VivoModels: Identification of Targets and New Modalities for Therapeutic Intervention

“…Up-regulation of PPA1 also enhanced proliferation, invasion and reduced pro-apoptotic JUN-kinase (JNK) signaling in A2780 cells (43). It was shown that the role of PPA1 in energy metabolism is to promote progression of malignant tumors (44). PPA1-mediated dephosphorylation was found to positively regulate the activity of yes-associated protein 2 (YAP2), promoting survival and DDP-resistance of EOC cells (45).…”

Molecular Insights into the Breast and Prostate Cancer Cells in Response to the Change of Extracellular Zinc

“…Among 12 annexin A isoforms (annexin A1-11 and annexin A13), annexin A5 in particular has unphosphorylated short N-terminus which enables this protein to exhibit a wide range of functions such as signalling, cancer cell growth, and invasion [74]. Te overexpression of both inorganic pyrophosphatase (PPA1) and tubulin α1c (TUBA1C) in response to the variation of exogenous zinc in MCF-7 cells (Table 1) suggests that high intracellular zinc promotes the metabolic activity of breast cancer cells, since inorganic pyrophosphatase is involved in cell metabolism, and tubulin α1c promotes glycolysis in breast cancer [75][76][77]. In addition, current fnding demonstrates that heat shock 70 kDa protein was overexpressed in MCF-7 cells (Table 1), correlating well with its overexpression at the gene level [78].…”

The inorganic pyrophosphatases of microorganisms: a structural and functional review

“…One example is the role of the PPi in tumor biology, which has been addressed extensively. Evidence suggests that it is an essential housekeeping enzyme that is overexpressed in tumors and is a key player in cell signaling, both in the regulation of its activation and in the role of tumor cell metabolism ( Wang et al, 2022 ). The overexpression of c-PPase in tumors can potentially be targeted by anticancer drugs ( Niu et al, 2021 ; Menteş & Yandım, 2023 ).…”