A new study by researchers at the University of Kentucky identifies a novel function of the enzyme spermine synthase (SMS) to facilitate colorectal cancer growth. SMS is an enzyme that produces spermine from spermidine, which has been shown to be important for cell growth. However, excessive accumulation of spermidine can have harmful effects on cell viability.
How cancer cells maintain a relatively high level of spermidine but below the toxic threshold to facilitate tumour growth is not well understood. Subsequently, a group led by the Markey Cancer Center researcher, Qing-Bai She, a professor in the UK College of Medicine's Department of Pharmacology and Nutritional Sciences, discovered that SMS is overexpressed in colorectal cancers and plays an important role in balancing cellular spermidine levels that are a necessary adaptation for colorectal cancer growth. The study, 'Spermine synthase and MYC cooperate to maintain colorectal cancer cell survival by repressing Bim expression', published in Nature Communications,
The group further revealed a link between the signalling of SMS and the oncogene MYC, a gene that plays a role in many cancer types, to maintain colorectal cancer cell survival. The study showed that combined inhibition of SMS and MYC signalling induced cancer cell death and tumour regression, which could be a promising strategy for colorectal cancer therapy.
"Our findings provide an in-depth understanding of how the polyamine metabolic pathway interacts with oncogenic signalling pathways in tumorigenesis and highlight the unmet need of clinically effective SMS inhibitors for the targeted therapy," said She.
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