One possible culprit for immortality in human cancer cells is the presence of human telomerase reverse transcriptase (hTERT) activity. The correlation between hTERT’s enzymatic activity and TERT expression levels in cancer has yet to be fully understood, but – building on previous work that established hTERT phosphorylation at threonine 249 (p-hTERT) in specific liver and pancreatic cancers – a Japanese research team has now identified that phosphorylated hTERT is common in many cancers with more aggressive characteristics.
The team developed a mouse monoclonal antibody capable of recognizing phosphorylated hTERT at threonine 249, reportedly the first effective tool for visualizing hTERT-RdRP in cancer through formalin-fixed, paraffin-embedded tissues. They then analyzed 1,523 cancer specimens with a variety of sites of origin to better understand the clinicopathological characteristics of hTERT-RdRP-active cancer.
The results showed that p-hTERT is associated with higher overall risk in aggressive lung, pancreatic, and liver cancers – regardless of TNM staging. Expression of p-hTERT is also strongly associated with “markers of squamous cell differentiation and aggressive features,” indicating that this process is common in aggressive cancers. The team discovered that p-hTERT is associated with a number of oncological features such as “adenosquamous carcinoma (lung and pancreas), invasive type of cancer (lung), high serum alpha-fetoprotein level (liver), and triple-negative status (breast)” (1).
Though p-hTERT may have prognostic value in lung, pancreatic, and liver cancers, this was not evidenced in colon and stomach cancers. The team also discovered that, although p-hTERT expression increased alongside mitosis score in all of the aforementioned cancers, expression in colon and stomach cancers decreased as pathological grade increased. One potential reason for this difference is that other mechanisms, possibly in the tumor microenvironment, may regulate p-hTERT expression in these cancers.
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References
- Y Matsuda et al., J Pathol, 257, 172 (2022). PMID: 35094384.