APR 09, 2020 6:07 AM PDT

The Unexpected Anti-Cancer Effects of the Human Telomerase

WRITTEN BY: Jasper Cantrell

The research to find effective treatments and diagnosing tools in the fight against cancer has led to a thorough investigation into the genetics behind cancer transformation and progression.  Genes linked to cancer progression are given the name oncogenes. Many oncogenes are often mutations in genes that affect cellular proliferation. The human telomerase reverse transcriptase (hTERT) is one example, and mutations in this gene are found in over 50 human cancers and are associated with tumor development and a poor prognosis. A group from Japan began an investigation into the link between a specific mutation in hTERT and cancer.

HTERT normally complexes with telomeres during the S-phase. The group had previously reported novel RNA dependent RNA polymerase (RdRP) activity and hTERT’s increased expression upon entrance to mitosis. A common source of protein activation is the phosphorylation of key residues, and this investigation shows the phosphorylation of threonine 249 (T249) to be essential for RdRP activity but not telomerase activity. Analysis of patient data showed mutations in T249 that prevented proper phosphorylation were a sign of prolonged overall survival.

Hoping to elaborate on why this phosphorylation of T249 on hTERT exhibits anti-cancer effects, they began in vitro and in vivo testing. Mutating T249 to abolish its phosphorylation in pancreatic and liver cancer cell lines, the group found that telomerase activity was maintained but the RdRP activity was substantially impaired. Grafting cancer cell lines with and without mutated T249 into mice showed that when hTERT was not phosphorylated, there was a severe impairment to tumor development with only two of eight mice developing tumors, and both tumors having severely impaired growth compared to controls. The investigation continued into the link between hTERT RdRP activity and the profound tumor suppression effects seen so far.

The group ran a screen for binding partners of hTERT, and a protein called forkhead box protein O4 (FOXO4) was found to bind to phosphorylated hTERT, but not unphosphorylated hTERT. FOXO4 is a transcription factor that controls gene expression and, in previous studies, has been linked to tumor suppression in certain cancers. Upon Identification of this interaction, the group proposed a model that hTERT phosphorylation allows the binding of FOXO4 mRNA, preventing its expression. Mutations in T249 prevent phosphorylation and allows FOXO4 to be expressed, which effectively eliminated tumor growth in mice models.

The group concludes, “We found that phosphorylation of hTERT at T249 regulates the expression of the tumor suppressor gene, FOXO4, in cancer cell lines”. Further investigation is, of course, needed. The newly identified interaction is quite an attractive target for anti-cancer treatments. After all, the nearly complete suppression of tumor growth is a great place to start for any potential therapy.

Sources: Nature, AlphaMed Press

About the Author
  • Hey everyone! My name is Jasper and, considering I am pretty new here to Labroots, I figured I would introduce myself. I received my bachelor’s from the University of California at Riverside back in 2016. I started off my career a few years ago with a job at a University over in New York, before moving over into the industry. I'm happy to be writing content for Labroots, and I hope you enjoy it!
You May Also Like
JUL 08, 2021
Genetics & Genomics
Is It Possible to Prevent Leukemia in Down Syndrome Patients?
JUL 08, 2021
Is It Possible to Prevent Leukemia in Down Syndrome Patients?
Children with Down syndrome have a significantly higher likelihood myeloid leukemia occurring in the first five years of ...
JUL 23, 2021
Cancer
Repurposed Antibiotics Show Promise Against Skin Cancer
JUL 23, 2021
Repurposed Antibiotics Show Promise Against Skin Cancer
In experiments with mice, researchers from the Netherlands have found that some antibiotics may be effective in tre ...
JUL 26, 2021
Genetics & Genomics
A Region of Non-Coding DNA That May Help Regulate Telomere Length is ID'ed
JUL 26, 2021
A Region of Non-Coding DNA That May Help Regulate Telomere Length is ID'ed
Many types of cells have to be replenished continuously throughout our lives, and the genome in the nucleus of those cel ...
AUG 23, 2021
Cancer
A Safe and Effective Combination Therapy for Advanced Cancer
AUG 23, 2021
A Safe and Effective Combination Therapy for Advanced Cancer
Immunotherapies are emerging as a promising strategy for the treatment of late-stage cancers which currently have m ...
SEP 18, 2021
Genetics & Genomics
Cancer Genes Might Aim for the Immune System, Not Growth Promotion
SEP 18, 2021
Cancer Genes Might Aim for the Immune System, Not Growth Promotion
The DNA in our cells can accumulate damage over may years. Environmental influences like UV light or cigarette smoke may ...
NOV 09, 2021
Microbiology
Can This Cat Parasite Become a Tumor Treatment?
NOV 09, 2021
Can This Cat Parasite Become a Tumor Treatment?
You may have heard of Toxoplasma gondii because it is so common. Cats carry this parasite, and anyone that cleans a litt ...
Loading Comments...