Tight Coordination of Protein Translation and Heat Shock Factor 1 Activation Supports the Anabolic Malignant State

Abstract

A unifying characteristic of aggressive cancers is a profound anabolic shift in metabolism to enable sustained proliferation and biomass expansion. The ribosome is centrally situated to sense metabolic states but whether it impacts systems that promote cellular survival is unknown. Here, through integrated chemical-genetic analyses, we find that a dominant transcriptional effect of blocking protein translation in cancer cells is complete inactivation of heat shock factor 1 (HSF1), a multifaceted transcriptional regulator of the heat-shock response and many other cellular processes essential for tumorigenesis. Translational flux through the ribosome reshapes the transcriptional landscape and links the fundamental anabolic processes of protein production and energy metabolism with HSF1 activity. Targeting this link deprives cancer cells of their energy and chaperone armamentarium thereby rendering the malignant phenotype unsustainable.

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Cite this paper

@inproceedings{Santagata2014TightCO, title={Tight Coordination of Protein Translation and Heat Shock Factor 1 Activation Supports the Anabolic Malignant State}, author={Sandro S. Santagata and Marc L Mendillo and Yun-chi Tang and Aravind Subramanian and Casey C. Perley and St{\'e}phane P Roche and Bang Wong and Rajiv Narayan and Hyoungtae Kwon and Martina I. Koeva and Angelika Amon and Todd R. Golub and John A Porco and Luke Whitesell and Susan Lindquist}, year={2014} }