Date of Graduation
8-2014
Document Type
Thesis (MS)
Program Affiliation
Biomedical Sciences
Degree Name
Masters of Science (MS)
Advisor/Committee Chair
Mien-Chie Hung Ph.D.
Committee Member
Paul J. Chiao Ph.D.
Committee Member
Min Gyu Lee Ph.D.
Committee Member
Zhen Fan M.D.
Committee Member
Jeffrey T. Chang Ph.D.
Abstract
MET is one of the receptor tyrosine kinases (RTKs) that are overexpressed in malignant cancer types, including breast cancer. While RTKs are traditionally known for their roles in signaling transduction from the cell surface, recent studies have provided evidence demonstrating that most of RTKs can translocate into nucleus to regulate cellular processes in response to both ligand and stress stimulation. Oxidative stress is a common stress in cancer cells due to alteration of metabolism, and constitutive oxidative stress related to reactive oxygen species (ROS) has been observed in breast cancer cells. Here, we show that hepatocyte growth factor (HGF) as well as hydrogen peroxide (H2O2) can induce nuclear translocation of full-length MET holoreceptor via a membrane-bound vesicle transport mechanism in breast cancer cells. Our findings provide a putative mechanism by which breast cancer cells adapt to oxidative stress.
Keywords
MET, oncogene, nuclear transport, breast cancer, hepatocyte growth factor receptor, ROS