Actin Cytoskeleton Remodelling in Apoptosis-induced Proliferation and Tissue Growth Control

点击翻译按钮获取中文摘要

In multicellular organisms including humans, damaged or stressed cells are removed by apoptosis, a programmed cell death pathway, to prevent their detrimental effects on the hosts. Studies in the past decade have revealed that dying cells, before they are removed, can signal their neighbouring surviving cells to induce extra cell divisions and production of new cells which compensates for the loss of dead cells. This process, critical for balancing cell numbers and maintenance of tissue homeostasis, is termed as Apoptosis-induced Proliferation (AiP). Uncontrolled AiP contributes to the development of diseases including cancer. It is therefore important to understand how AiP is controlled at the cellular and molecular level. By using Drosophila as a genetic model organism, we observed an increase of actin filaments, fundamental components of the cellular scaffolding structure - cytoskeleton, in cells emitting AiP signals. Interestingly, such an increase of actin filaments, i.e. actin remodelling, is required for production of reactive oxygen species (ROS) and activation of c-Jun N-terminal kinase (JNK) signalling, two key processes known to trigger AiP. The proposed work is to determine how actin remodelling is regulated in apoptotic dying cells and how it controls ROS production and JNK activation leading to AiP. We will also examine roles of actin remodelling in the development of malignant tumour. Dissecting the molecular control of actin remodelling and its cellular functions in both AiP and tumourigenesis will significantly impact our understanding of physiological tissue recovery and pathological tumour development.