Gasotransmitters in cancer metastasis: insights from the biology of carbon monoxide, nitric oxide, and hydrogen sulfide.

Over the past decade, growing attention has focused on the interplay between gasotransmitters and cancer progression. These gaseous molecules exert diverse effects on inflammation, angiogenesis, redox balance, and cellular movement, making them influential players in tumor metastasis. This review explored the emerging roles of gasotransmitters (carbon monoxide, nitric oxide, and hydrogen sulfide) in driving solid tumor metastasis, highlighting the molecular mechanisms involved. In addition, it delineated key signaling pathways implicated in metastatic spread, such as mitogen-activated protein kinase, phosphoinositide 3-kinase/protein kinase B pathway, signal transducer and activator of transcription 3 and nuclear factor κB, offering critical insights into gasotransmitter regulation. This analysis highlights that the gasotransmitter pro/anti-metastatic effects are dependent on enzymatic source, cellular context and concentration. Overall, this review summarizes the pathways implicated in metastasis of different cancer types and emphasizes the need for more targeted approaches to inhibit gasotransmitter signaling in cancer.