Photo Credit: Magicmine

The following is a summary of “Mechanism of PFK-1 in the occurrence and development of bladder cancer by regulating ZEB1 lactylation,” published in the March 2024 issue of Urology by Wang et al.

Bladder cancer (BC) stands as a prevalent malignancy within the genitourinary system, necessitating comprehensive exploration to elucidate its underlying mechanisms. Phosphofructokinase 1 (PFK-1), a vital constituent of the PFK family, is pivotal in orchestrating cancer metabolism, particularly through lactylation modification. Zinc finger E-box-binding homeobox 1 (ZEB1), recognized as an oncogenic driver across various cancer types, emerges as a focal point in this investigation, aimed at unraveling the intricate interplay between PFK-1 and ZEB1 lactylation in the context of BC pathogenesis.

Employing a multifaceted approach, this study embarked on deciphering the ramifications of PFK-1 modulation on ZEB1 lactylation dynamics within BC development. Researchers unraveled the intricate molecular interplay governing BC progression by utilizing established methodologies, including cell viability assays via the CCK-8 kit, coupled with assessments of glucose utilization and lactate production employing specialized assay kits. Their findings unveiled a noteworthy elevation in ZEB1 expression levels within bladder cancer cells, establishing its pivotal role in disease pathogenesis. Furthermore, modulation of PFK-1 expression demonstrated profound impacts on BC cellular behavior, manifesting in inhibited proliferation, migration, and invasion, alongside discernible suppression of tumor growth in vivo models.

Delving deeper into the mechanistic underpinnings, the study group delineated the pivotal role of PFK-1 in modulating glycolytic processes within BC cells, evident through attenuated glucose consumption, reduced lactate production, and perturbed extracellular acidification rates upon PFK-1 knockdown. Importantly, their investigation unearthed a novel regulatory axis wherein PFK-1 exerts regulatory control over histone lactylation, thereby modulating the transcriptional activity of ZEB1 within BC cells.

In summation, the study underscores the significant role of PFK-1 in mitigating the malignant phenotype of BC cells through its regulatory influence on ZEB1 lactylation. These insights shed light on the intricate molecular landscape governing BC pathogenesis and pinpoint PFK-1 as a prospective therapeutic target in managing this debilitating disease. Consequently, the findings pave the way for exploring innovative therapeutic avenues, offering renewed hope for patients grappling with BC and underscoring the potential of PFK-1 modulation as a promising therapeutic strategy in BC management.

Source: bmcurol.biomedcentral.com/articles/10.1186/s12894-024-01444-5