Colon tumour cell death causes mTOR dependence by paracrine P2X4 stimulation.

ABSTRACT: Solid cancers exhibit a dynamic balance between cell death and proliferation ensuring continuous tumour maintenance and growth^1,2. Increasing evidence links enhanced cancer cell apoptosis to paracrine activation of cells in the tumour microenvironment initiating tissue repair programs that support tumour growth^3,4, yet the direct effects of dying cancer cells on neighbouring tumour epithelia and how this paracrine effect potentially contributes to therapy resistance are unclear. Here we demonstrate that chemotherapy-induced tumour cell death in patient-derived colorectal tumour organoids causes ATP release triggering P2X4 (also known as P2RX4) to mediate an mTOR-dependent pro-survival program in neighbouring cancer cells, which renders surviving tumour epithelia sensi

SUBMITTER: Schmitt M 

PROVIDER: S-EPMC7613947 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature