title: RB1-mediated cell-autonomous and host-dependent oncosuppressor mechanisms in radiation-induced osteosarcoma.
abstract: The mechanisms by which retinoblastoma 1 (RB1) mediates oncosuppressive functions are still being elucidated. We found that radiation-induced senescence in the bone depends on RB1 and is associated with the secretion of multiple bioactive factors, including interleukin-6 (IL-6), as well as with the infiltration of natural killer T (NKT) cells. Importantly, the inhibition of RB1, IL-6 or NKT cells predisposed mice to radiation-induced osteosarcomas, unveiling a cancer cell-extrinsic mechanisms that underlie the oncosuppressive activity of RB1.
authors.affiliation: Peter MacCallum Cancer Centre; Sarcoma Genomics and Genetics Laboratory, Research Division; Melbourne, VIC Australia.
authors.forename: Maya
authors.initials: M
authors.lastname: Kansara
authors.affiliation: Peter MacCallum Cancer Centre; Sarcoma Genomics and Genetics Laboratory, Research Division; Melbourne, VIC Australia ; The Kinghorn Cancer Centre and Garvan Institute; Sydney, NSW Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Thomas
keywords: interleukin-6; natural killer T cells; radiation; retinoblastoma 1; senescence; senescence-associated secretory phenotype (SASP)