LB1011 Oncogenic ras mutation induces spatiotemporally specific tissue deformation through converting fluctuated into sustained ERK activation

Tissue regeneration and maintenance rely on coordinated stem cell behaviors. This orchestration can be impaired by oncogenic mutations leading to tissue architecture disruption ultimately cancer formation. However, it is still largely unclear how oncogenes perturb cells’ functions break architecture. Here, we utilized intravital imaging novel signaling reporter investigate the mechanisms of Kras-induced in hair follicle. Through longitudinally tracking same follicles live mice, found KrasG12D, a mutation that lead squamous carcinoma, induces epithelial deformation spatiotemporally specific manner. linked with spatial dysregulation proliferation migration follicle regeneration. By using mouse allows capture real-time ERK signal dynamics at single level animal, discovered KrasG12D converts transient fluctuation cells into sustained activation. In contrast, carrying HrasG12V, which does not disrupt tissue, exhibit fluctuated Furthermore, combining drug treatment longitudinal imaging, demonstrated inhibiting reverts KrasG12D-induced deformation, suggesting alteration led Kras mutant. Intriguingly, low number were insufficient induce activation deform collective effect from large group mutant required for disruption. Altogether, our work supports niche-dependent mechanism oncogene-induced Oncogenic abnormalities when conditions are met, disturb local coordination through altering dynamic communications.