ZIP1⁺ fibroblasts protect lung cancer against chemotherapy via connexin-43 mediated intercellular Zn²⁺ transfer.

ABSTRACT: Tumour-stroma cell interactions impact cancer progression and therapy responses. Intercellular communication between fibroblasts and cancer cells using various soluble mediators has often been reported. In this study, we find that a zinc-transporter (ZIP1) positive tumour-associated fibroblast subset is enriched after chemotherapy and directly interconnects lung cancer cells with gap junctions. Using single-cell RNA sequencing, we identify several fibroblast subpopulations, among which Zip1⁺ fibroblasts are highly enriched in mouse lung tumours after doxorubicin treatment. ZIP1 expression on fibroblasts enhances gap junction formation in cancer cells by upregulating connexin-43. Acting as a Zn²⁺ reservoir, ZIP1⁺ fibroblasts absorb and transfer Zn²⁺

SUBMITTER: Ni C 

PROVIDER: S-EPMC9547061 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature