Cadmium, Cellular Senescence, and Cancer

Cadmium (Cd) is an environmentally widespread toxic heavy metal with adverse effects on human health. Exposure to Cd is almost unavoidable in the modern-day world, and humans are most commonly exposed to Cd via contaminated food and drinking water, occupational inhalation, and cigarette smoking. Cellular senescence is characterized by the acquisition of senescence-associated secretory phenotype (SASP) and permanent cell cycle arrest, which is triggered by various types of stresses. Depending on the physiological context, cellular senescence can be beneficial or detrimental. In regard to cancer, senescence is a potent tumor suppressor mechanism, but on the other hand, it paradoxically fuels tumorigenesis. Based on the known mechanism of action of Cd, it is likely that Cd exposure is involved in cellular senescence and aging-related tumorigenesis. Here, we summarize and discuss the current knowledge regarding the interconnected relationships between Cd exposure, senescence, and cancer from three main aspects of Cd toxicity that have not been focused on previously: micronutrient homeostasis, SASP, and telomere length. This review encourages further investigation into the emergent research theme of Cd cytotoxicity.