Regulation of TP63α/sonic hedgehog axis in n-dimethylnitrosamine-induced liver cancer stem cells

25^th WORLD CANCER CONFERENCE

October 19-21, 2017 | Rome, Italy

Hongyu Han, Xiaoqian Wang, Xiaoting Li and Caiyun Zhong

Sun Yat-sen University Cancer Center, China
Nanjing Medical University, China

Posters & Accepted Abstracts: J Cancer Sci Ther

Abstract :

Nitroso-compounds are critical dietary risk factor of liver cancer. Cancer stem cells (CSCs) play a significant role in the formation and development of cancer. To date, the action of nitroso-compounds on the induction of liver CSCs as well as the underlying mechanisms has not been defined. In the present study, we revealed that chronic N-nitroso dimethylamine (NDMA) exposure induced malignant transformation of human normal liver cells. We further showed that NDMA-induced malignant transformed liver cells exhibited CSCs properties, as evidenced by increased sphere formation capacity in serumfree-medium culture, dramatically elevated expression of liver CSCs markers and increased number of CD133+ cells, along with upregulation of TAp63�±, downregulation of ��Np63�±, and activation of Sonic Hedgehog pathway. Moreover, we illustrated that suppression of Sonic Hedgehog activity inhibited NDMA-induced liver CSCs properties; over expression of TAp63�± activated Sonic Hedgehog pathway and promoted liver CSCs activity, whereas down expression of TAp63�± inhibited Sonic Hedgehog and suppressed liver CSCs; an opposite action of ��Np63�± on Sonic Hedgehog pathway and liver CSCs was demonstrated. Taken together, our data suggested for the first time the vital role of TP63�±/Sonic Hedgehog axis in regulating NDMA-induced liver CSCs, and thus could provide new insights into the molecular mechanisms of liver carcinogenesis as well as its target intervention.

Biography :

Hongyu Han has completed her PhD from Sun Yat-sen University Cancer Center in 2010. She was a research scientist in University of Pennsylvania and Fox Chase Cancer Center during 2014-2016. Currently, she is a Scientist in the Department of Nutrition in Sun Yat-sen University Cancer Center. Her research interests focus on the effects and mechanisms of dietary factors and cancer development. She has published more than 10 papers in reputed journals.