The Reprogramming of Tumor Stroma by HSF1 Is a Potent Enabler of Malignancy
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Lindquist_The reprogramming.pdf
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Author(s)
Scherz-Shouval, Ruth
Santagata, Sandro
Mendillo, Marc L.
Sholl, Lynette M.
Ben-Aharon, Irit
Beck, Andrew H.
Dias-Santagata, Dora
Stemmer, Salomon M.
Whitesell, Luke
Koeva, Martina I
Date Issued
May 2014
Journal
Cell
Publisher
Elsevier
Citation
Scherz-Shouval, Ruth et al. “The Reprogramming of Tumor Stroma by HSF1 Is a Potent Enabler of Malignancy.” Cell 158.3 (2014): 564–578.
Version
Author's final manuscript
Abstract
Stromal cells within the tumor microenvironment are essential for tumor progression and metastasis. Surprisingly little is known about the factors that drive the transcriptional reprogramming of stromal cells within tumors. We report that the transcriptional regulator heat shock factor 1 (HSF1) is frequently activated in cancer-associated fibroblasts (CAFs), where it is a potent enabler of malignancy. HSF1 drives a transcriptional program in CAFs that complements, yet is completely different from, the program it drives in adjacent cancer cells. This CAF program is uniquely structured to support malignancy in a non-cell-autonomous way. Two central stromal signaling molecules—TGF-β and SDF1—play a critical role. In early-stage breast and lung cancer, high stromal HSF1 activation is strongly associated with poor patient outcome. Thus, tumors co-opt the ancient survival functions of HSF1 to orchestrate malignancy in both cell-autonomous and non-cell-autonomous ways, with far-reaching therapeutic implications.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cell.2014.05.045
