"Head and neck squamous cell carcinoma (HNSCC) ranks sixth worldwide for cancer-related mortality. Research in cancer biology has led to the discovery that many cancers, including HNSCC, appear to be supported by cells that have stem cell like properties. Further, CD44+ population was identified as cancer stem cells in Head and Neck Squamous cell carcinoma. These cancer stem cells have the ability to self-renew, differentiate and develop resistance against chemotherapeutic agents preventing complete elimination of tumor. It was shown these stem cells show abnormal Wnt/B-catenin signaling.

Breast cancer is classified into four subtypes in clinic as ER+ (luminal A or luminal B, usually PR+/− Her2−),overexpressed Her2 (Her2+, usually ER−PR−), negative for ER, PR, and Her2 (ER−PR−Her2−, mostly basal-like) i.e. Triple negative, and normal-like. In breast cancer, showed a small subset of population (CD44+ CD24low/-) that are highly tumorigenic. These cells are termed as Cancer-stem cells (CSC). Owing to heterogeneity nature of these cells, it will be crucial to identify the homogenous population that perhaps could be beneficial in targeted cancer therapy.

Signaling pathways such as Wnt/Notch/Sonic hedgehog regulate stem-cell renewal, and genes affected in these pathways are associated with oncogenesis. Our objective is to study the molecular and cellular mechanisms that govern the stem cell regulation and how the perturbation in these mechanisms leads to oncogenesis. In our study, we will select the genes of Wnt/Sonic-hedgehog/ Notch signaling pathways those are involved in stem cell regulation and cancers. The knock out/conditional knock out and transgenic mice in the above mentioned pathways will be studied.

Enhancing factor (EF), a growth factor modulator, is the mouse homologue of human secretory group II phospholipase A2. EF in the presence of EGF (Epidermal growth factor) has been shown to give cells a growth advantage, and is known to play a role in phenotypic transformation of normal cell in vitro. EGF interacts with EF and is known to be involved in stem cell regulation. This suggests that EF may have a role in stem cell regulation. In these K14-EF mice, we would like to delineate the role of EF in epidermal stem cell regulation.