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In Silico Study of STAT3 and its Role in MMP Mediated Metastasis

Sunil Kanti Mondal, Samyabrata Mukhoty

Metastasis is one of the major reasons for cancer associated deaths. Constitutive activation of Signal Transducer and Activator of Transcription 3(STAT3) by a variety of the factors, such as Cytokines and Growth factors within the cytoplasm, from where it is transported into the nucleus and promote the transcription of various anti-apoptotic and metastatic genes like MMP2, MMP7, MMP9, as a transcription factor and leads to several different forms of Cancers.

Multiple Sequence Alignment and Jalview analysis reveals that the human STAT3 is highly conserved, with no changes along the entire length of the human STAT3 protein and maintaining close resemblance with the selected organisms. The aim of our systematic study is to identify the residues of STAT3 interacts with its nuclear transporter protein Importin and the promoter of MMP genes. So that specific inhibitor can be designed, this will block the identified interacting sites of STAT3. Furthermore, finding for interacting proteins of STAT3, MMP2, MMP7 and MMP9 from String database and differential expression studies of STAT3 and the respective MMP2, MMP7 and MMP9 in different organs led us to conclude that specific drug molecules has to be designed to block the interacting sites of STAT3 to overcome the metastatic spread of cancers by these MMPs. The Virtual screening studies by targeting the amino acid residues of STAT3 responsible for interacting with the promoter of MMPs led us to conclude that the small molecule Deferoxamine is able to be fruitful in minimizing the cancer associated metastatic spread.