biostudies-literatureLex KHoward Hughes Medical InstituteFondation pour la Recherche MédicaleMinistry of Education and Science | Fundação para a Ciência e a Tecnologia15066-15074https://www.ebi.ac.uk/biostudies/studies/S-EPMC7334448biostudies-literatureUnknown117(26)Cancer incidence increases exponentially with age when human telomeres are shorter. Similarly, telomerase reverse transcriptase (<i>tert</i>) mutant zebrafish have premature short telomeres and anticipate cancer incidence to younger ages. However, because short telomeres constitute a road block to cell proliferation, telomere shortening is currently viewed as a tumor suppressor mechanism and should protect from cancer. This conundrum is not fully understood. In our current study, we report that telomere shortening promotes cancer in a noncell autonomous manner. Using zebrafish chimeras, we show increased incidence of invasive melanoma when wild-type (WT) tumors are generated in <i>tert</i> mutant zebrafish. Tissues adjacent to melanoma lesions (skin) and distant organs (intestine) in <i>teProceedings of the National Academy of Sciences of the United States of AmericaTelomere shortening produces an inflammatory environment that increases tumor incidence in zebrafish.PMC7334448LISBOA-01-0145-FEDER-022170SPF201809007006SFRH/BD/52173/2013PTDC/BIM-ONC/3402/2014PTDC/SAU-ONC/116821/2010IECSMaia Gil MGiannetti KLex KLopes-Bastos BCarvalho TMarzullo MFigueira MFerreira MGfalseTelomere shortening produces an inflammatory environment that increases tumor incidence in zebrafish.Cancer incidence increases exponentially with age when human telomeres are shorter. Similarly, telomerase reverse transcriptase (<i>tert</i>) mutant zebrafish have premature short telomeres and anticipate cancer incidence to younger ages. However, because short telomeres constitute a road block to cell proliferation, telomere shortening is currently viewed as a tumor suppressor mechanism and should protect from cancer. This conundrum is not fully understood. In our current study, we report that telomere shortening promotes cancer in a noncell autonomous manner. Using zebrafish chimeras, we show increased incidence of invasive melanoma when wild-type (WT) tumors are generated in <i>tert</i> mutant zebrafish. Tissues adjacent to melanoma lesions (skin) and distant organs (intestine) in <i>te2020-01-01T00:00:00Z2020 Jun2026-07-15T23:26:14.993Z2025-06-01T12:00:19.497ZS-EPMC73344483255449210.1073/pnas.1920049117