Crucial role of breast cancer tumor suppressor revealed

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Cells with low levels of protein profilin 1 in breast tumors have an increased capacity to metastasize and invade other tissues, according to research published in European Cell Biology (2014; doi:10.1016/j.ejcb.2014.12.002).

In recent years, medical professionals have been greatly interested in the development of new treatments to combat metastasis, which is the largest cause of death in patients with breast cancer.

However, effective treatments have still not been developed to stop or prevent tumor cells spreading from their primary tumor, which is a critical step in the cancer reaching different organs during metastasis.

Now, a new study led by José Javier Bravo-Cordero, PhD, a Spanish researcher working in the Albert Einstein College of Medicine in New York, New York, reveals how the profilin 1 protein intervenes in the formation of determining structures for the tumor invasion.

"To obtain this level of effectiveness, the tumor cells form a subcellular structure called invadopodia (from the Latin invado, invade, and podio, feet; invasive feet) and they use it to spread towards other parts of the organism," explained Bravo-Cordero.

Using high-resolution microscope techniques, the authors have been able to study the dynamics of the invadopodia in tumor cells which lack profilin 1, and describe their role and the route they regulate.

They found that patients with breast cancer tumors show reduced levels of the protein profilin 1, which is related to an increased capacity for metastasis to other organs.

"Surprisingly, the cells which lack profilin 1 show extremely invasive activity mediated by the invadopodia, compared to control cells. It is as if we had taken the brake off and lost control of the vehicle," described Bravo-Cordero.

What is more, he added, "In the absence of profilin 1, the invadopodia are more aggressive when it comes to degrading the extracellular matrix and are highly invasive structures, which explains the high metastatic potential of these cells."

The work, carried out with the collaboration of researchers from the University of Pittsburgh in Pennsylvania, shows the importance of the internal structure of the invadopodia and the actin cytoskeleton. They also revealed how profilin 1 plays a vital role in regulating actin.

"If we destroy the [actin] scaffolding, the structures do not form; in the same way if we are very efficient with the assembly of this scaffolding we can form structures that have more invasive capacity. These are the variables that we have to play with to stop invasive tumors, and profilin 1 regulates this balance," said Bravo-Cordero.

The authors described the molecular route that allows the invadopodia to be more aggressive in the cells that lack profilin 1. This route plays a role in their maturation for these to be efficient.

“All the invasive machinery is being revealed at a subcellular level, and we are identifying the 'nuts and bolts' we must adjust to prevent tumor cells from spreading. This will greatly assist in developing new treatments which may help to halt the process of metastasis," concluded the authors.

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