After Pune scientists identified a crucial gene (SMAR1) that suppresses tumours, further exploring its role has helped them undertake pathbreaking research that could be a gamechanger in the treatment of cancer.
Dr Samit Chattopadhyay, senior scientist, National Centre for Cell Science and his team have now shown how this gene is a master regulator of cells and can help prevent the spread of breast cancer. The research has been published in the Proceedings of the National Academy of Sciences (PNAS) a top journal the United States National Academic of Sciences in June this year.
This gene encodes a protein that functions as a tumour suppressor and cell regulator. Since Chattopadhyay first identified the SMAR1 protein, work done from his lab is known worldwide. “A defect in this gene puts an individual at risk of prostate, breast, colon and oral cancers. The advanced grades of breast cancer infact indicated that there was less of SMAR1 protein,” Chattopadhyay told media persons on Tuesday.
In our new research we found that CD44 (a cell surface molecule involved in cell proliferation) protein gets altered in cancer cells. This further signals other cancerous cells to spread and the CD44 variables are also implicated in the resistance of cancer stem cells to chemotherapeutic drugs. Now here a master regulator cell prevents the formation of the CD44 variables and hence restricts the generation of cancer stem cells, Chattopadhyay said.
The CD44 variables occur due to alternative splicing and here the NCCS group saw that loss of SMAR1 gene helps generate CD44 protein which spreads cancerous cells. “Based on our observations we are now conducting experiments using plant based compounds to restore SMAR1 gene and restrict CD44 splicing,” Chattopadhyay added.
In yet another significant research, NCCS scientist Dr Manas Santra has helped show the way on developing a promising molecule that can minimise the side effects of chemotherapy. His research which has also been published in PNAS this year focuses on tumour suppressor p53 – also known as guardian of the genome. They have shown for the first time how p53 gets activated to kill cancer cells upon receiving cancer therapy. “We have found a gene – an F-box protein FBXO31 – which suppresses the cancer promoting gene MDM2- and hence important to p53. Once the growth of cancer promoting gene is arrested, the p53 levels increase and this research could be useful in designing a more effective cancer therapy,” explained Santra.