The mechanism of PFK-1 in the occurrence and development of bladder cancer by regulating ZEB1 lactylation

• Published in: BMC urology 2024-03, Vol.24 (1), p.59-59, Article 59
• Main Authors: Wang, Rong, Xu, Fei, Yang, Zhengjia, Cao, Jian, Hu, Liqi, She, Yangyang
• Format: Article
• Language: English
• Subjects: Acidification; Antibodies; Bladder cancer; Cancer; Cancer therapies; Cell adhesion & migration; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell viability; Cholecystokinin; Dextrose; DNA binding proteins; Enzymes; Gene Expression Regulation, Neoplastic; Genetic aspects; Glucose; Glucose metabolism; Glycolysis; Health aspects; Histones; Homeobox; Humans; Kinases; Lactates; Lactic acid; Lactylation; Malignancy; Medical prognosis; Metabolism; Metastasis; Oncology, Experimental; PFK-1; Phenotypes; Phosphofructokinase; Phosphofructokinase-1 - genetics; Phosphofructokinase-1 - metabolism; Proteins; Urinary Bladder Neoplasms - pathology; ZEB1; Zinc Finger E-box-Binding Homeobox 1 - genetics; Zinc Finger E-box-Binding Homeobox 1 - metabolism; Zinc finger proteins
• ISSN: 1471-2490; 1471-2490
• DOI: 10.1186/s12894-024-01444-5

Bladder cancer (BC) is one of the most common malignancies of the genitourinary system. Phosphofructokinase 1 (PFK-1) is one of member of PFK, which plays an important role in reprogramming cancer metabolism, such as lactylation modification. Zinc finger E-box-binding homeobox 1 (ZEB1) has been demonstrated to be a oncogene in many cancers. Therefore, this study was performed to explore the effects of PFK-1 on the lactylation of ZEB1 in BC development. Cell viability was measured using the CCK-8 kit. The glucose assay kit and lactate assay kit were used to detect glucose utilization and lactate production. The DNA was purified and quantified by qRT-PCR. In the present study, we found that ZEB1 expression levels were significantly elevated in bladder cancer cells. Impaired PFK-1 expression inhibits proliferation, migration, and invasion of BC cells and suppresses tumour growth in vivo. We subsequently found that knockdown of PFK-1 decreases glycolysis, including reduced glucose consumption, lactate production and total extracellular acidification rate (ECAR). Mechanistically, PFK-1 inhibits histone lactylation of bladder cancer cells, and thus inhibits the transcription activity of ZEB1. Our results suggest that PFK-1 can inhibit the malignant phenotype of bladder cancer cells by mediating the lactylation of ZEB1. These findings suggested PFK-1 to be a new potential target for bladder cancer therapy.