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Dr Skourides talks to CNA about potential of a protein in cancer treatment
CNA - Athena Arsalidou - CYPRUS/Nicosia 30/10/2013 13:16

  Although the Laboratory of Developmental Biology and Nanobiotechnology at the University of Cyprus does not focus on cancer research, it has made significant research in the field of embryology, which could possibly help in the treatment of cancer.

 In an interview with CNA, Head of the Laboratory, Assistant Professor Dr Paris A. Skourides, talked about the breakthrough that was made by his research team, the results of which were recently published in the scientific journal ‘Development.’

 “This work was centered on exploring the role of a protein called FAK in the development of the embryo and specifically its role in morphogenesis. This protein was known to be essential in embryonic development but its precise role was not understood”, he said.

Dr Skourides noted that to determine the role of FAK, they generated a novel inhibitor which is very effective in blocking FAK’s function and which allowed them for the first time to probe the role of FAK during gastrulation.

“Our results show that FAK has a critical role in morphogenesis and its activity is required for a specific morphogenetic movement called epiboly. Defects in epibloy lead to arrest of gastrulation, severe morphological and tissue positioning abnormalities and embryonic death” he said.

Through this work, they also shed light on the mechanical integration of individual morphogenetic movements i.e how one movement is coupled to others giving rise to the three dimensional architecture of the embryo.

Asked how those findings could contribute to the fight against cancer, he said that while normal tissues have very low levels of FAK, tumors significantly overexpress this protein.

Specifically several studies have established FAK as a prominent determinant in cancer initiation, progression and metastasis.
“For this reason, FAK is being actively pursued as a possible therapeutic target, a fact that has motivated the development of FAK inhibitors as anti-cancer drugs”, he pointed out.

According to Dr Skourides, the expression of a previously characterized protein inhibitor of FAK called FRNK, was shown for example to suppresses both tumor growth and metastasis in mice.
“The new protein inhibitor we designed, called FF, has proved to be far more potent than FRNK both in cultured cells as well as in the embryo suggesting that it would be a good candidate to explore further as a therapeutic agent”, he stressed.
Asked if there is any additional ongoing research by the Laboratory on cancer, he said that they are currently in the process of testing the potential of FF as a therapeutic agent.

“Although cancer research is not a major focus of our group the potency of the new inhibitor prompted us to explore its potential in this setting. We are comparing the effects of FF expression to those of the previously characterized inhibitor (FRNK) to determine if the high potency of FF in blocking FAK function translates in a high efficiency of suppressing tumor growth and metastasis”, he underlined.

The initial research on the FAK’s role was financed by the European Commission with the Marie Curie Fellowship and the continuation of the research was financed by the Cyprus Research Promotion Foundation. First results are expected in six months.

The study will initially focus on a particular type of cancer, but as Dr Skourides explained, since the inhibitor seems to have the ability to inhibit cell migration in various types of cells and since cell migration is essential for metastasis, theoretically research could involve a number of cancer types.

Referring to the overall work of the Laboratory, he told the Cyprus News Agency that it is generally focused on embryonic development and nanotechnology applications in biology.

“A number of specific proteins like the Focal Adhesion Kinase, Paxillin, intergins and calpain2 are currently under investigation”, he said.
Dr Skourides noted that one of the major areas of study is the elucidation of the mechanisms responsible for generating the three dimensional architecture of the vertebrate embryo.

“All embryos begin as a fertilized egg which after several cell divisions, basically becomes a ball of cells. This ball of cells somehow has to morph into a recognizable embryo with a head, trunk, extremities etc. The way this is achieved is through massive and precisely orchestrated movements of the cells. This period in the development of the embryo is called gastrulation and the cell movements shaping the embryo are called morphogenetic movements (from the Greek words morphi and genesis)”, he explained.

He described this as a crucial time for the developing embryo not only because defective gastrulation will lead to congenital morphological abnormalities, but in addition, because organogenesis (the formation of organs like the heart, liver etc) is dependent on the correct positioning of tissues which is achieved through gastrulation.

“This in effect means that defects in morphogenesis can also lead to defective organ formation in the embryo. The critical role of gastrulation in embryonic development is perhaps best summarized in the words of Lewis Wolpert, a pioneering embryologist, who said It is not birth, marriage, or death, but gastrulation, which is truly the most important time in your life."

Dr Skourides said that the study of gastrulation and morphogenetic movements demands cutting edge imaging since one has to be able to visualize these processes in the living embryo.

“This is where the second major area of research in our lab comes in, which basically is the use of nanotechnology to generate probes that can improve our imaging abilities. Specifically, we work with Quantum Dots (nano-meter sized crystals that emit light allowing their visualization), developing applications for these nano-devices in biology”, he pointed out.

Asked about the achievements of the laboratory, he told CNA that one of the early achievements of his group was the development of the first method that allows the conjugation of Quantum Dots (QDs) to target proteins inside the living embryo.

“This work, which made the cover of the journal of Nanobiotechnology, was a continuation of work done at The Rockefeller University where the first biocompatible QDs where synthesized”, he said.

He went on to say that later, his group was able to target several proteins with QDs in living embryos simultaneously, allowing the visualization of protein movements inside the cells of living embryos.

Overall, he explained, this work was the first demonstration that nano-devices can be specifically conjugated (attached) to proteins inside cells and embryos allowing targeting of such devices to specific cellular compartments or molecular complexes.

With respect to the embryological investigations, some of the major findings include the determination of the role of FAK in mesoderm migration and the discovery that a protease (an enzyme that cleaves proteins) called calpain2, is crucial for gastrulation.

More recently the group also became involved in the study of ciliogenesis (the formation of cells with whip-like appendages, necessary for both embryonic development and also involved in a number of human diseases termed ciliopathies) when we described the role of a protein called Nubp1 in ciliogenesis in a paper that made the cover of the highly regarded journal Developmental Biology.

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