Rajiv Kumar Jha
Accepted Abstracts: J Cancer Sci Ther
Cyr61 is a 42 kDa secreted protein from CCN-family, containing four different conserved molecular domains. Overproduction of Cyr61/CCN1 plays a critical role in the development and progression of pancreatic cancer, through the induction of EMT and stemness. Pancreatic cancer stem ce-lls (PCSC) are rare tumour cells characterized by their ability to self-renew, and are responsible for tumour recurrence accompanied by resistance to current therapies. Shh pathway is highly activated in pancreatic CSCs and plays important role in maintaining stemness by regulating the expression of stemness genes. Cyr61 expression has been found to be exorbitantly higher in cancer stem/tumour initiating Panc-1-side-population (SP) cells. Cyr61/CCN1 silencing in pancreatic CSCs results in reduced aggressive behaviour, reversing of the EMT, blocking of the expression of stem-cell-like traits and inhibition in migration. In contrast, addition of Cyr61 protein in culture medium augments EMT and stemness features in relatively less aggressive BxPC3 pancreatic cancer cells. The objective of this study is to investigate the role of CCN1 & Shh pathway in pancreatic cancer and to examine the molecular mechanisms by which CCN1 acts as a regulator for Shh pathway. Another objective of this study is to examine the molecular mechanisms by which resveratrol inhibits stem cell characteristics of pancreatic CSCs derived from human primary tumours and KrasG12D transgenic mice. Hence, this study aims to identify the role of CCN1 in pancreatic cancer and the possibility of resveratrol to be used as a therapeutic agent.