Putting A Cap On Cancer Cell Division

Scientists in Singapore have discovered a molecular pathway that limits the division of HPV-induced cervical cancer cells.

AsianScientist (Dec. 12, 2017) – A team of researchers in Singapore has identified a molecular pathway that suppresses virus-induced cancers. They published their findings in PLOS Pathogens.

Some cancers are known to be caused by viral infections. For example, two strains of the human papillomavirus (HPV) are responsible for up to 70 percent of cervical cancer cases. The virus causes abnormal cell growth by inserting its genetic material into the cells of the cervix.

Uncontrolled cell growth is typically prevented by the shortening of telomeres—protective caps on the ends of chromosomes. Each time a cell divides into two, the telomeres get shortened, and the cell eventually stops dividing. Cancer cells, however, are known to bypass this limit by producing telomerase, an enzyme that extends the length of telomeres. In HPV-infected cells, the protein TIP60 is known to prevent progression to cervical cancer, but the interactions between TIP60 and telomerase remain unknown.

In this study, researchers at the Cancer Science Institute of Singapore (CSI Singapore) and the National University of Singapore (NUS) examined the regulation of telomerase by TIP60 in virus-induced cancer cells. The team discovered that TIP60 inhibits telomerase by interacting with and modifying a partner molecule, Sp1.

When TIP60 modifies Sp1, Sp1 can no longer bind to the regulatory sequences of the telomerase gene to activate it. This results in less production of telomerase, which prevents the cancer cells from continuous division. The identification of this molecular pathway opens a new window of hope for therapeutic interventions against cancers.

“Our findings hold exciting potential in the fight against a range of virus-induced cancers, including cervical cancer, liver cancer and Burkitt’s Lymphoma,” said study corresponding author Dr. Sudhakar Jha, a principal investigator at CSI Singapore.

“Given that 85 percent of cancers are triggered by high amounts of telomerase, our study, which lends a deeper insight into the inhibition of telomerase by TIP60, could also be applied to other groups of cancer such as breast, colorectal and ovarian cancer. Our next step is therefore to investigate the influence of this new pathway in these other groups of cancer,” he added.



The article can be found at: Rajagopalan et al. (2017) TIP60 Represses Telomerase Expression by Inhibiting Sp1 Binding to the TERT Promoter.

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Source: National University of Singapore; Photo: Shutterstock.
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