Research ArticleCancer

Intercellular transmission of the unfolded protein response promotes survival and drug resistance in cancer cells

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Sci. Signal.  06 Jun 2017:
Vol. 10, Issue 482, eaah7177
DOI: 10.1126/scisignal.aah7177

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Stress signals improve tumor fitness

Mechanisms that promote the survival of healthy cells are often exploited by tumor cells. Tumors experience increased cellular stress, and targeting the endoplasmic reticulum (ER) stress response, an adaptive response to increased protein translation, has been proposed as an anticancer therapy. Rodvold et al. found that prostate cancer cells undergoing an ER stress response transmit some signal to cocultured, naïve cancer cells that then also launch an ER stress response. This phenomenon, which the authors call “transmissible ER stress” (TERS), promoted faster tumor growth and resistance to common anticancer drugs in xenograft mouse models. The findings show that tumor cells leverage this intrinsically adaptive stress response to enhance the fitness of the overall tumor. Inhibiting this signal (once identified) or the pathways induced in the recipient cells might avert drug resistance in prostate cancer patients.