Role of Hippo pathway in promoting invasion and metastasis of liver cancer cells by oxygenated polycyclic aromatic hydrocarbons
Due to the presence of oxygenated functional groups,oxygenated polycyclic aromatic hydrocarbons(oxy-PAHs)possess higher polarity,solubility,mobility,and biological reactivity than their parent PAHs,and are more widely distributed in the environment.Although numerous oxy-PAHs exhibit heightened genotoxicity,carcinogenicity,and developmental toxicity,limited research has been conducted to elucidate the underlying mechanisms responsible for their tumorigenic promotion.Notably,the Hippo-YAP pathway has emerged as a pivotal regulatory process governing cancer cell immunity,proliferation,and metastasis.In this study,the tumor promoting effect of oxy-PAHs(specifically 9-Fluorenone)that are commonly found in the environment,as well as the underlying Hippo-YAP regulation mechanism were investigated by using the liver cancer cell exposure model.The results showed that a high concentration of 9-Fluorenone exposure significantly enhanced the invasion,migration,and epithelial-mesenchymal transition(EMT)of HepG2 cells,and the Hippo-YAP pathway was identified as playing a crucial role in the tumor-promoting process.Specifically,9-Fluorenone exposure can induce dephosphorylation of upstream kinases in the Hippo pathway,such as MST and LATS,and then induce dephosphorylation of YAP.Consequently,YAP is able to bind to TEAD in the nucleus,thereby regulating the occurrence of EMT and ultimately promoting the invasion and metastasis of cancer cells.This study contributes valuable toxicological evidence supporting the tumor-promoting effect of oxy-PAHs and holds significant reference value for the comprehensive assessment of the ecological and health risks associated with PAHs and their derivatives.
oxygenated polycyclic aromatic hydrocarbonsinvasion and metastasisHippoEMT
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