PgmNr Z6002: Optical Control of Cancer Initiation in Zebrafish.

Authors:
Zhiping Feng 1 ; Vriz Sophie 2 ; Michel Volovitch 2,3 ; Ludovic Jullien 4 ; Shuo Lin 5 ; Shimon Weiss 1,6 ; David Bensimon 6,7


Institutes
1) Department of Molecular, Cellular and Integrative Physiology, UCLA, USA; 2) Collège de France, Center for Interdisciplinary Research in Biology, France; 3) Department of Biology, ENS, France; 4) Department of Chemistry, ENS, France; 5) Department of Molecular, Cell and Developmental Biology, UCLA, USA; 6) Department of Chemistry and Biochemistry, UCLA, USA; 7) Laboratoire de Physique Statistique, ENS, France.


Abstract:

Although cancer initiation and evolution have been extensively studied, they are not, as of yet, fully understood. In particular, two outstanding questions, the effectiveness of oncogenic transformation and the role of the local microenvironment on cancer initiation, require the investigation into early events of cancer initiation and the study of the fates of individual cells and their progenies. Several models have attempted to answer how cancer arises from individual transformed cells. However, current probes of cancer development are restricted to the collective properties of many thousands of cells. Recently, we developed a technology that allows for the control of protein activity and gene expression in single cells through light activation. In this work, we utilize this method to activate in a small number of cells in a live zebrafish a typical oncogene, K-RasG12V, and investigate effects of these changes on tumorigenesis under varied genetic backgrounds. We successfully demonstrated the spatiotemporal control of oncogene expression in live zebrafish. Furthermore, we investigated different tumorigenic phenotypes by transiently or permanently activating K-Ras at varied developmental stages. We believe that our studies could shed new light on cancer initiation and growth and provide new tools for target validation and testing of novel anti-cancer drugs.