A Tumor Suppressor Gene Is Discovered to Prevent Metastasis for the First Time

Cancer’s fundamental cause is mutations in genes controlling cells. Effective treatment development depends on identifying their roles in cancer. In November 2016, Journal of Molecular Cell Biologypublished a study identifying the tumor suppressor gene TIP60’s role in preventing breast cancer cell metastasis.

Tumor suppressors are one of 3 gene types involved in cancer. They normally prevent excessive proliferation and are damaged in most human cancers. Recently, their relationship with metastasis, beyond suppressing proliferation, has also been studied.

TIP60 is a DNA repair protein found mutated in colon, lung, breast, pancreatic, stomach and skin cancers. TIP60 protein is synthesized according to TIP60 gene information. Advanced genetic analyses examined how tumor-suppressing TIP60 protein prevents breast cancer cell metastasis.

According to the Research Results:

• TIP60 protein controls the activity of two proteins called DNMT1 and SNAIL2.

Examining these two proteins:DNMT1is an enzyme managing epigenetic mechanisms. By adding methyl groups to genes, it reduces gene activity. DNMT1 activity is very high in many cancers, causing loss of tumor suppressor activity.SNAIL2 protein is involved in epithelial–mesenchymal transition and programmed cell death, apoptosis. Epithelial–mesenchymal transition enables cancer cells to spread to other tissues and organs.

• When TIP60 protein mutated, DNMT1 levels rose and DNMT1 activity consequently increased. Cancer cells became more aggressive and metastasized to other tissues.

What Does This Study Mean Clinically?

• This is the first study explaining the TIP60 tumor suppressor gene’s role in metastasis.
• An important breast cancer drug target was discovered. Previous studies found very low TIP60 protein activity in patients with poor disease course. Low TIP60 activity was also identified in colon and uterine cancers, suggesting a potential target in other cancers.
• An important result is that TIP60 may be a biomarker for disease course. Strategies could maintain TIP60 activity at normal or high levels. Inhibitors increasing TIP60 activity are being developed.
• Gene therapies could also increase TIP60 gene activity, replacing damaged TIP60 with healthy TIP60.

Recent research found high TIP60 protein activity increases chemotherapy efficacy, suggesting future use in combination treatments.