[Research Advances in the Pulmonary Carcinogenic Effects of Atmospheric Fine Particulate Matter Mediated by GPER].

Abstract

Lung cancer remains the leading cause of cancer-related death worldwide. Fine particulate matter (PM2.5), classified as a group I human carcinogen, has been extensively linked to lung cancer development through epidemiological studies. The G protein-coupled estrogen receptor (GPER) can be activated and induce tumorigenesis by environmental pollutants, and it is significantly overexpressed in lung cancer tissues, highlighting its critical role in disease progression. Research indicates that environmental estrogen-like components and metal ions in PM2.5 can activate GPER, thereby regulating downstream signaling pathways such as mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT). This activation triggers inflammatory responses, oxidative stress, and ferroptosis, ultimately promoting tumor cell proliferation, apoptosis, migration, epithelial-mesenchymal transition, and remodeling of the tumor microenvironment. Collectively, these mechanisms drive the initiation and progression of lung cancer. In summary, GPER serves as a pivotal molecular hub connecting PM2.5 exposure to lung cancer pathogenesis, presenting a promising therapeutic target. Inhibitors targeting GPER may offer novel strategies for the prevention and treatment of lung cancer.
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