International Congress on
Structural Biochemistry, Stem Cells and Molecular Biology

Biography:

Chanakya N Kundu, professor at School of Biotechnology, KIIT University, Bhubaneswar, completed his PhD in Biochemistry from the Indian Institute of Chemical Biology, Kolkata Jadavpur, India. In prior to join at  KIIT University he worked as a post doc at Texas A&M University, Texas, USA,  Florida Shands Cancer Center, Gainesville, USA and Cleveland Clinic Foundation, Cleveland, Ohio, USA in the field of cancer biology. Currently the focus of his research work is to understand the molecular mechanism of metastasis, angiogenesis in cancer stem cell signaling. He has developed a new chemotherapeutic cocktail which not only inhibits the bulk of cancer cells but also inhibit the cancer stem cell proliferation, angiogenesis as well as reduce the inflammation in cancer patients. He has already published more than 65 peer reviewed research articles in national and international journal, file four patents, multiple book chapter, etc. He is the recipient of multiple award/recognition from the national and international level such as international young investigator award, Dr Kunti and Omprakash oration award, DBT-CREST,etc   He is serving as an editorial board member in multiple journal such as Plos One,  etc.

Abstract:

Although NECTIN-4 ( a pvrl-4 encoded gene) has been reported as a junction protein for decades with recent reports of its advocacy in cancer biology, there remains a paucity of studies exploring its detailed functional significance in metastasis, angiogenesis and cancer stem cells. We report, NECTIN-4 as a probable marker for breast cancer stem cells and provide experimental evidence suggesting that it upregulates WNT/β-CATENIN signaling via PI3K/AKT axis as the self renewal pathway for breast cancer stem cells. Using highly metastatic breast cancer cells and human umbilical vein endothelial cells (HUVECs), we have  also demonstrated the contribution of NECTIN-4 to angiogenesis. We also provide in-depth in ovo, in vitro, in vivo and ex vivo evidence that NECTIN-4 causes metastasis and angiogenesis and propose that nectin-4 is a biomarker both the processes in breast cancer. Following hypoxia, the expression of ADAM-17 in metastatic breast cancer stem cells (mBCSCs) causes the shedding of the ecto-domain of NECTIN-4 into the microenvironment, which physically interacts with integrin-β4 specifically on endothelial cells. This interaction promotes angiogenesis via the Src, PI3K, AKT, iNOS pathway and not by Phospho-Erk or NF-κβ pathways. In vitro, in ovo and in vivo induction and abrogation of an angiogenesis cascade in the presence and absence of the NECTIN-4 ecto-domain, respectively, confirms its role in angiogenesis. Thus, disrupting the interaction between NECTIN-4 ecto-domain and integrin-β4 may provide a means of targeting mBCSC-induced metastasis and angiogenesis.