PM2.5-associated nitro-PAH exposure promotes tumor cell metastasis through Hippo-YAP mediated transcriptional regulation

Abstract

Extensive epidemiological studies have revealed that nearly 25% of the premature mortality from lung cancer is attributed to regional haze caused by a high level of fine particulate matter (PM2.5). The nitro-PAHs (NPAHs), with a lower volatility, are more likely to be absorbed with PM2.5 and to pose a threat to health, whereas there is insufficient information about carcinogenesis caused by NPAHs. Our study evaluated the carcinogenic effect of typical NPAHs on lung cancer cell adhesion and metastasis and revealed the possibly involved mechanism through in vitro experiments. For the specific mechanism, typical NPAHs could directly induce the inactivation of serine/threonine kinase (MST1/2) and large tumor suppressor (LATS1/2) and result in the nuclear translocation of Yes-associated protein (YAP). The nuclear YAP would then combine with TEA domain transcription factor (TEAD) and profoundly influence the transcription of migration and adhesion genes related to lung cancer metastasis. These findings remind us of the possible carcinogenicity of NPAHs absorbed with PM2.5 and provide a reference for the prevention and mitigation of tumorigenesis in a heavily polluted environment.