Abstract
Ionizing radiation (IR) is used to treat half of all cancer patients because of its ability to kill cells. IR, however, can induce stem cell-like properties in non-stem cancer cells, potentiating tumor regrowth and reduced therapeutic success. We identified previously a subpopulation of cells in Drosophila larval wing discs that exhibit IR-induced stem cell-like properties. These cells reside in the future wing hinge, are resistant to IR-induced apoptosis, and are capable of translocating, changing fate, and participating in regenerating the pouch that suffers more IR-induced apoptosis. We used here a combination of lineage tracing, FACS-sorting of cells that change fate, genome-wide RNAseq, and functional testing of 42 genes, to identify two key changes that are required cell-autonomously for IR-induced hinge-to-pouch fate change: (1) repression of hinge determinants Wg (Drosophila Wnt1) and conserved zinc-finger transcription factor Zfh2 and (2) upregulation of three ribosome biogenesis factors. Additional data indicate a role for Myc, a transcriptional activator of ribosome biogenesis genes, in the process. These results provide a molecular understanding of IR-induced cell fate plasticity that may be leveraged to improve radiation therapy.
Highlights
More than half of cancer patients receive ionizing radiation (IR), alone or as a component of their treatment
Ionizing radiation (IR) is used to treat half of all cancer patients because of its ability to kill cells but treatment failures are common because tumors grow back
We asked which changes in the properties of cells facilitate regeneration in Drosophila after exposure to radiation
Summary
More than half of cancer patients receive ionizing radiation (IR), alone or as a component of their treatment (www.cancer.org). Regenerate the tumor, leading to treatment failure. Regeneration of tumors is attributed to cancer cells with stem cell-like properties [1,2]. These cells, distinguished by cancer type-specific markers such as CD44 and ALDH for Head and Neck Squamous Cell Carcinoma, survive treatment and show elevated capacity to initiate tumors compared to their counterparts that lack the markers [3,4]. There is evidence for non-stem cells acquiring stem cell-like properties in the context of regeneration of normal tissues after radiation damage. There is mounting evidence that IR can induce cell fate plasticity, but the mechanisms remain to be fully understood
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