Cell competition overcomes host tissue resistance to unleash tumour growth in a Drosophila brain cancer model

Primary tumours of the central nervous system are extremely aggressive and often incurable. While tumours are known to interact with their microenvironment, how the interplay between tumour cells and the host tissue controls tumour progression remains elusive. We addressed this question in a Drosophila model of cancer stem cell-driven tumour which originates during development and grows extensively within a network of cortex glia cells (CG) through adulthood. We found that tumour growth induces progressive remodeling of the CG network and leads to CG apoptosis through cancer stem cell-driven competition, a process which in turn unleashes tumour growth. Notably, preventing CG death reduces tumour growth, revealing a resistance capacity within the CG. Transcriptional profiling of CG cells at different stages revealed a biphasic response, featuring an early specific signature followed by a later collapse of essential cellular functions and pathways, including the conserved JNK pathway. JNK signalling in CG normally plays a neuroprotective role and initially hinders tumour progression, providing resistance. However, its subsequent downregulation eventually brings the collapse of the host tissue, ultimately curbing tumour growth. This study uncovers a dynamic and complex interplay between host tissue resistance and tumour-driven competition, which shapes tumour progression.