Profilin1 Study Advances Understanding of Breast Cancer Metastases

Alejandra Valenzuela-IglesiasMedicalResearch.com Interview with:
Alejandra Valenzuela-Iglesias
Ph.D. candidate
Department of Molecular Biology
University of Sonora Hermosillo, Sonora

MedicalResearch: What is the background for this study? What are the main findings?

Response: Breast cancer is one of the leading causes of cancer death in women all around the world. In recent years, there has been great interest in creating new therapies that will help to prevent or stop metastasis, but the therapies developed up until today are not completely effective. Metastasis is the main cause of death for a cancer patient because it implies that tumor cells have detached from the primary tumor and have colonized in one or more vital organs or tissues in the organism. For this to occur, the invasive tumor cells form actin-driven membrane protrusions called invadopodia. These protrusions possess proteolytic activity to degrade the basal membrane and extracellular matrix, which facilitates metastatic cancer cells to enter the bloodstream and spread to distant organs in the body. It has been shown that any dysregulation in the actin cytoskeleton leads to impaired invadopodia formation.

Profilin1, an actin and phosphoinositide binding protein, is downregulated in several adenocarcinomas.

Our study was a collaboration between Albert Einstein College of Medicine, University of Pittsburgh, and University of Sonora, lead by Dr. Jose Javier Bravo-Cordero and published in the European Journal of Cell Biology. We showed for the first time the role of profilin1 in invadopodia formation and function in human breast cancer cells MDA-MB-231. By using cell imaging techniques we unveiled the dynamic of the profilin1-depleted cells, finding that profilin1 can act as a negative regulator of breast cancer cell invasion, acting as a break in invadopodia turnover, by modulating the molecules involved in invadopodia maturation. The removal of profilin1 expression accelerates invadopodia maturation rate, explaining the invasive phenotype previously reported for this type of cells.

MedicalResearch: What should clinicians and patients take away from your report?

Response: Invadopodia are key subcellular structures during dissemination of metastasis that help tumor cells to escape from the primary tumor and reach the blood vessels to travel to distant organs. Our findings help to understand invadopodia regulation and could be used to develop new therapies to prevent invadopodia formation and therefore cancer metastasis.

picture is a MDA-MB-231 cell, immunostained with tks5 and cortactin as invadopodia markers (the picture is showing the merge and the invadopodia are the punctiform structures in the center of the cell)

MDA-MB-231 cell, immunostained with tks5 and cortactin as invadopodia markers (the picture is showing the merge and the invadopodia are the punctiform structures in the center of the cell)

MedicalResearch: What recommendations do you have for future research as a result of this study?

Response: In the present day, we are in a very exciting moment for cancer research, because there has been a great number of investigations revealing how the invasive machinery of metastasis works and the molecules that are involved. We encourage continued unveiling of the invadopodia machinery with hopes that in the near future an effective anti-metastasis therapy can be created.

Citation:

Profilin1 regulates invadopodium maturation in human breast cancer cells

Valenzuela-Iglesias A1, Sharma VP2, Beaty BT3, Ding Z4, Gutierrez-Millan LE5, Roy P6, Condeelis JS7, Bravo-Cordero JJ8.

Eur J Cell Biol. 2015 Feb;94(2):78-89. doi: 10.1016/j.ejcb.2014.12.002.
Epub 2014 Dec 31.

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MedicalResearch.com Interview with:, & Alejandra Valenzuela-Iglesias (2015). Profilin1 Study Advances Understanding of Breast Cancer Metastases MedicalResearch.com