E-GEOD-45852 - Tight coordination of protein translation and heat shock factor 1 activation supports the anabolic malignant state [ChIP-Seq]
Released on 21 July 2013, last updated on 5 September 2013
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. We used ChIP-Seq to examine affect of rocaglates and cycloheximide on HSF1 genomic occupancy in MCF7 and M0-91 cancer cells.
Marc Mendillo <email@example.com>, Angelika Amon, Aravind Subramanian, Bang Wong, Casey C Perley, Hyoungtae Kwon, John A Porco, Luke Whitesell, Marc L Mendillo, Martina Koeva, Rajiv Narayan, Sandro Santagata, Stéphane P Roche, Susan Lindquist, Todd R Golub, Yun-chi Tang
Tight coordination of protein translation and HSF1 activation supports the anabolic malignant state. Santagata S, Mendillo ML, Tang YC, Subramanian A, Perley CC, Roche SP, Wong B, Narayan R, Kwon H, Koeva M, Amon A, Golub TR, Porco JA Jr, Whitesell L, Lindquist S. , Europe PMC 23869022