The following is a summary of “APIP regulated by YAP propels methionine cycle and metastasis in head and neck squamous cell carcinoma,” published in the February 2024 issue of Oncology by Li et al.
The Yes-associated protein (YAP) is a pivotal regulator in tumor progression and metabolic reprogramming. Yet, its precise involvement in head and neck squamous cell carcinoma (HNSCC) metabolic alterations remains elusive. Leveraging RNA sequencing coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry, the investigation unveils a profound influence of YAP on the methionine metabolism pathway in HNSCC. Specifically, researchers observe that YAP orchestrates a robust upregulation of key metabolites and enzymes integral to methionine metabolism. Notably, their study identifies a novel link between YAP and activating a crucial enzyme in the methionine salvage pathway, namely, aminoacyl tRNA synthetase complex-interacting multifunctional protein (APIP).
Subsequent functional assays elucidate the pivotal role of APIP in driving HNSCC cell migration and invasion in vitro and facilitating tumor metastasis to both regional lymph nodes and distant organs in vivo. Mechanistically, the study group unveils that APIP-mediated enhancement of the methionine cycle potentiates HNSCC metastasis through the phosphorylation-mediated inactivation of glycogen synthase kinase 3 beta (GSK3β), thereby inducing the epithelial-mesenchymal transition pathway. Furthermore, the clinical correlation studies underscore the clinical relevance of these findings, demonstrating elevated APIP expression and heightened levels of methionine cycle metabolites in HNSCC patients, particularly in those with lymph node metastasis. Collectively, the comprehensive findings illuminate APIP as a novel downstream target of YAP, shedding light on its pivotal role in fueling the methionine cycle and driving HNSCC metastasis through GSK3β phosphorylation-mediated mechanisms.
These insights advance the understanding of HNSCC pathogenesis and offer potential therapeutic avenues targeting the metabolic vulnerabilities of this aggressive malignancy.
Source: sciencedirect.com/science/article/abs/pii/S0304383524001496