Competition for Space Induces Cell Elimination through Compaction-Driven ERK Downregulation.

Area of Science:

• Developmental Biology
• Cell Biology
• Cancer Research

Background:

• Tissue plasticity depends on cell survival and growth regulation in response to environmental cues, including mechanical forces.
• Epithelial compaction can induce cell death, potentially contributing to tissue homeostasis and pre-tumoral cell expansion.
• Pathways triggering apoptosis due to tissue deformation and the role of compaction-driven death in clone expansion remain poorly understood.

Purpose of the Study:

• To investigate the pathways that trigger apoptosis in response to tissue deformation.
• To assess the contribution of compaction-driven death to pre-tumoral clone expansion in vivo.
• To explore the role of mechanical cues in regulating cell survival and tissue morphogenesis.

Main Methods:

• Utilized the Drosophila pupal notum model.
• Developed and employed a novel live sensor for ERK activity.
• Investigated the effects of tissue compaction on cell elimination and pathway signaling.
• Assessed the impact of oncogene Ras activation on neighboring cell apoptosis and clone expansion.

Main Results:

• Tissue compaction induces cell elimination by downregulating the epidermal growth factor receptor/extracellular signal regulated kinase (EGFR/ERK) pathway and upregulating the pro-apoptotic protein Hid.
• The EGFR/ERK pathway's sensitivity to mechanical forces may broadly regulate cell elimination during morphogenesis and tissue homeostasis.
• Activation of the oncogene Ras in clones downregulates ERK and induces apoptosis in neighboring cells via compaction, facilitating Ras clone expansion.

Conclusions:

• Mechanical modulation of the EGFR/ERK pathway during compaction is a key mechanism for cell elimination.
• Compaction-driven apoptosis contributes to the expansion of pre-tumoral clones.
• Understanding these mechanical signaling pathways is crucial for comprehending tumor progression and tissue development.