Abstract
Deciphering effective ways to suppress tumor progression and to overcome acquired apoptosis resistance of tumor cells are major challenges in the tumor therapy field. We propose a new concept by which tumor progression can be suppressed by manipulating tumor cell identity. In this study, we examined the effect of ER stress on apoptosis resistant tumorous cells in a Caenorhabditis elegans germline tumor model. We discovered that ER stress suppressed the progression of the lethal germline tumor by activating the ER stress sensor IRE-1. This suppression was associated with the induction of germ cell transdifferentiation into ectopic somatic cells. Strikingly, transdifferentiation of the tumorous germ cells restored their ability to execute apoptosis and enabled their subsequent removal from the gonad. Our results indicate that tumor cell transdifferentiation has the potential to combat cancer and overcome the escape of tumor cells from the cell death machinery.
Highlights
A major challenge in the tumor therapy field is the development of new strategies to eliminate tumors and cancer cells
We consistently detected SYTO12-labeled corpses in tumorous gonads of gld-1 RNAi-treated animals exposed to ER stress induced either by genetic means or by chemical means (Figure 1A,B and Figure 1—figure supplement 1)
We conclude that ire-1 is not required for germ cell transdifferentiation per se. It is required for germ cell transdifferentiation in response to ER stress. These findings indicate that the regulation of germ cell pluripotency by ER stress in gld-1-deficient animals requires the activation of the ER stress sensor IRE-1, and is not the result of interference with ER homeostasis and function
Summary
A major challenge in the tumor therapy field is the development of new strategies to eliminate tumors and cancer cells. Some aspects of tumorigenesis are exhibited in the gld-1 germline tumor model These include the ability of the tumorous germ cells to proliferate in a growth factor–independent manner (Francis et al, 1995a) and their regulation by genes homologous to known human oncogenes or human tumor suppressor genes (Pinkston-Gosse and Kenyon, 2007). Some precocious germ cell transdifferentiation into ectopic somatic cells has been reported to occur at a low frequency in gld-1-deficient animal (Ciosk et al, 2006) This transdifferentiation of the germ cells can be further enhanced by manipulation of RNA binding proteins, P granule components, transcription factors and histone modifiers; all of which regulate gene expression within the transdifferentiating germ
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
