Reshma Murali, Project Assistant (DST grant)
Deciphering the molecular circuitry of Cancer Stem Cells
Breast cancer is the most common type of cancer among women and has a significant health burden in India. Patient prognosis depends on the tumor subtype and impacts on therapeutic strategy. We have made rapid progress in the treatment of the ER+ and Her2+ subtypes of breast cancer. Unfortunately due to lack of expression of ER, HER2 and PR, we currently have no targeted therapy available for the Triple Negative Breast Cancer (TNBC) subtype. There also exists highly diverse intra-tumoural heterogeneity, with a subpopulation of tumour cells (termed Cancer Stem Cells/ CSCs) driving critical cancer phenotypes such as metastasis, self-renewal and chemoresistance. Effective therapeutic targeting of CSCs is essential for the complete eradication of a tumour and prevention of relapse in patients due to outgrowth of chemoresistant CSCs. Transcription factors are critical regulators of normal cellular differentiation and lineage commitment. The Inhibitor of Differentiation (ID) proteins are helix-loop-helix transcriptional repressors with established roles in stem cell self renewal, lineage commitment and niche interactions. Recent studies have demonstrated that Id1 is over expressed in the poor prognosis TNBC subtype, controls proliferation and is required for breast cancer cells to escape oncogene induced cellular senescence. Our hypothesis is that Id1 marks CSCs in a proportion of TNBCs, enabling us to prospectively isolate and dissect the biology controlling the phenotype of this unique subpopulation of cells. This will also helps us in the identification and analysis of pathways critical to CSC survival.