AKR1C3 mediates gastric cancer cell invasion and metastasis via the AKT and JNK/p-NF-κB signaling pathways

Autor: Liying Lin, Xinzhu Xiao, Xiaoxiong Guo, Canmei Zhong, Mingkai Zhuang, Jie Xu, Yin Wang, Fenglin Chen
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Scientific Reports, Vol 14, Iss 1, Pp 1-17 (2024)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-024-82039-w
Popis: Abstract Gastric cancer (GC) is globally recognized as the fifth most common cancer and the third leading cause of cancer-related mortality. Early metastasis in GC significantly contributes to its high mortality and unfavorable prognosis. However, the underlying mechanisms of this phenomenon remain largely unexplored. Among the various factors involved, AKR1C3 has emerged as a crucial component in the pathways of tumorigenesis and metastasis across multiple cancer types. Yet, the precise significance of AKR1C3 in GC patients’ prognosis and its role in GC progression remain elusive. This study illuminated the significant downregulation of AKR1C3 in GC tissues, linking it to an aggressive phenotype and poor prognosis. Interestingly, while AKR1C3 overexpression did not affect the proliferation of GC cells, it significantly inhibited their ability to invade and metastasize. The underlying mechanism appears to involve AKR1C3’s inhibition of the p-JNK pathway, which leads to reduced phosphorylation of IKKα/β and IKBα, lowering p-NF-κB levels and hindering its movement into the nucleus, thereby stifling the epithelial-mesenchymal transition (EMT) process in GC cells. These insights reveal AKR1C3’s tumor-suppressive effects in GC and suggest its potential as a diagnostic and prognostic biomarker, offering new avenues for targeted therapies in gastric cancer management.
Databáze: Directory of Open Access Journals
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