A new discovery in the field of medicine, in Spain, has led the researchers to the conclusion that VAV proteins may provide pharmacological targets for skin cancer.
Squamous cell carcinoma is the most common form of skin cancer, which although usually not life threatening in some cases can be aggressive and spread to other organs. So far not known signaling pathways that lead to the formation of this type of cancer.
A team of Spanish researchers, led by Dr the Cancer Research Center of Salamanca, Xosé R. Bustelo, has found that Vav proteins, some enzymes that determine the activation of signaling pathways related to cell proliferation, may provide drug targets for cancer and other skin diseases such as psoriasis.
Following a study in mice, have shown that a signaling pathway essential for the emergence and development of skin cancer is jointly controlled by Vav2 and Vav3 oncoproteins.
To demonstrate the effect of inactivation of these promoters in the disease, the authors used mice genetically modified to delete the expression of Vav2 and Vav3. The results appear in the latest issue of the journal PLoS-Biology.
For authors, this strategy was intended to simulate the effect of the systemic use of inhibitors against these two proteins would have on the initiation and progression of skin tumors and at the same time, assess the side effects that could result in inhibition normal skin tumor.
This allowed us to demonstrate experimentally that the elimination of proteins Vav3 Vav2 and induced a significant fall of the induced skin tumors in mice after topical application of various carcinogens, namely agents that induce tumors through mutation induction in the genome of the cells of the skin.
However, mice lacking these two proteins showed no alteration in the normal development of the skin, indicating that the use of inhibitors against these proteins specifically affect the viability of the tumor cells but not normal cells of patients with skin cancer.
Squamous cell carcinoma is one of the most common skin cancers both in Spain and in the rest of the world. Unlike other tumors, a correlation between the occurrence and application of certain medical treatments, such as for example the application of inhibitors against oncogenes (B-Raf) in antitumor therapies and procedures with some kind of antifungal drugs or immunosuppressants.
Therefore, its treatment may be interested not only in tumor therapy but also in prevention. However, much remains to elucidate the signaling pathways and biological processes that determine its appearance and subsequent development.
Subsequent studies conducted in animals and in their skin cells purified allowed explain why antitumor effect derived from the inactivation of these two proteins. Thus, it was found that the expression of these two proteins was necessary for the survival of tumor cells to agents that, like many of the drugs used in chemotherapy induce cell death through the induction of DNA damage.
In addition, researchers were able to show that the proteins Vav were also necessary for optimum proliferation of tumor cells and induction of other biological processes, such as local inflammation intratumoral create a ambientetisular favoring the growth and survival of tumor cells a more robust.
These experiments indicate that Vav3 Vav2 and play an important role in the initiation and development of skin cancers, to promote cell signaling pathways in cancer cells related to DNA damage cell survival, proliferation and tissue microenvironment modification wherein said cells grow and develop.
Vav proteins could be potential drug targets for various dermatological diseases.
Many of these programs are activated protumorigenic other common diseases of the skin, such as psoriasis. Therefore, the results suggest that the proteins Vav could represent potential drug targets for various dermatological diseases.
The researchers warn that these experiments have identified probably only the "tip of the iceberg" of the biological program, since their study has revealed the existence of other biological processes controlled by these oncoproteins that can assist in the process of tumor.
Thus, current evidence indicates that proteins Vav2 and Vav3 and appear to contribute to widespread reprogramming tumor tissue microenvironment modifying the behavior of various cell types 'healthy' near the tumor.velopment.
They have also found that these proteins contribute to normal cell functioning 'mother' tumor, responsible for maintenance and progression over time. All these new pathways are still under study by the research groups that participated in this study.
According to the authors, given the basic nature of this research, further studies are still needed long-term to develop effective chemical inhibitors against these proteins and to check if they actually work in the clinical setting.
This work was conducted with funding provided by the Ministry of Science and Innovation through the program of Biomedicine and Thematic Network of Cooperative Research in Cancer as part Xosé Bustelo, Jesus M. Paramio and Balbinus Alarcón. The Spanish Association Against Cancer also contributes to joint research and Bustelo and Alarcón.
Till soon, kind regards,
Luis.
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