The Role of TIMP-4 in Cervical Cancer Development

The Role of TIMP-4 in Cervical Cancer Development

In a recent study titled Tissue Inhibitor of Metalloproteinase-4 Triggers Apoptosis in Cervical Cancer Cells“, published in the PLoS ONE journal, researchers discovered a complex involvement of a specific metalloprotease, TIMP-4, in cervical cancer development.

Cancer can be defined as an abnormal process of cell growth which has the ability to invade other parts of the body. It can affect various parts of the body including the brain, kidneys, digestive system, lungs and skin. Cervical cancer is the third most commonly diagnosed cancer in women. It is characterized by an abnormal cell growth in the cervix, the lower part of the uterus. While practically no symptoms appear at early stages of cervical cancer, during advanced stages of the disease patients usually suffer from pain in the lower part of the abdomen, vaginal bleeding and discharge, weight loss due to lack of appetite, fatigue, back pain, swollen legs and even bone fractures.

Several factors have been implicated in the development of cervical cancer. These include infection with varying types of human papilloma virus (HPV), occurring in 75% of affected patients, active/passive cigarette smoking, long term use of oral contraceptives and multiple pregnancies. Nevertheless, the detailed mechanisms by which cervical cancer develops are unknown. In general, evolution of malignant cells is caused by accumulation of alterations in the genes responsible for controlling cell proliferation, death and up keeping of genetic integrity. As such, recent studies suggested a link between tissue inhibitors of metalloproteinases (TIMPs) and cancer development.

In this novel study, researchers showed that TIMP-4 has an amplifying effect on cell death deregulation in cervical cancer, thus controlling tumor development.

Metalloprotease is a protease enzyme which involves a metal in the catalytic mechanism. The TIMP family comprises four pleiotropic proteins (TIMP1TIMP2TIMP3 and TIMP4) that modulate the activity of matrix metalloproteinases (MMPs). In patients with cancer, these enzymes illustrate different and sometimes even opposing roles in cellular processes such as proliferation, invasion and deregulation of the process of cell death (so called, apoptosis).

For example, it has been reported that TIMP-4 is linked to breast and gastric cancer when its expression increases, whereas in brain and kidney cancers its expression is decreased.

The present study holds important future applications: if the mechanisms by which TIMP-4 influence tumor development are understood novel approaches and solutions in cancer therapy may be developed. The authors emphasize that future investigations are required to clarify the mechanisms of action and the exact role(s) of TIMPs in cervical cancer progression.

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Malika Ammam received her MS degree from the University of Pierre et Marie CURIE in July 2002 and her PhD from the University of Paris Sud XI, France in September 2005. From 2006 to 2007, she worked as a research fellow at the University of Kansas in collaboration with Pinnacle Technology Inc. (USA). From 2007 to 2010, she was a research associate at KU Leuven, Belgium. From 2010 to 2012, she worked at the University of Ontario Institute of Technology in collaboration with Alcohol Countermeasure Systems Corporation, Canada. She has also held the prestigious Rosalind Franklin fellowship.

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