The Reprogramming of Tumor Stroma by HSF1 Is a Potent Enabler of Malignancy (Cell 2014, 158:564-578)

報告日期: 2015/05/22
報告時間: 17:10/18:00
報告學生: 陳孟延
講評老師: 吳佳慶
附件下載: 下載[1484-1425859039-1.pdf] 

The Reprogramming of Tumor Stroma by HSF1 Is a Potent Enabler of Malignancy

Ruth Scherz-Shouval, Luke Whitesell,Susan Lindquist et al.

Cell 158, 564–578, July 31, 2014

Speaker: Meng-Yen, Chen                                        Time: 2015.05.22 PM0510

Commentator: Dr. Wu, Chia-Ching                            Place: Room 602


Cancer cells in a tumor mass are surrounded by a variety of other cell types as well as extracellular matrix components which comprised the tumor microenvironment. Cancer cells have to coevolution with microenvironment for tumor formation and progression1. Cancer associated fibroblasts (CAF), the most abundant cell in most tumor stroma having normal karyotype are recruited by the tumor to support cancer cell proliferation, angiogenesis, invasion, metastasis, and drug resistance. CAF also secret cytokines which feeds back to promote the fibroblast-to-CAF transition, through autocrine transforming growth factor b (TGF-b) and stromal-derived factor 1 (SDF1) signaling2. Heat shock factor 1 (HSF1) has been shown to play a fundamental role in cancer cells. The depletion of HSF1 markedly reduces growth, survival, and metastatic potential. In this article, authors ask if HSF1 plays a complementary, and perhaps equally important role in the tumor stroma by converting it to a protumorigenic state. Authors found that HSF1 activation is a key factor in the transcriptional reprogramming of the stroma from a tumor-repressive environment to a supportive one. And at least two central signaling pathways in the tumor microenvironment are empowered by HSF1: pathways mediated by TGF-b and by SDF1. They also establishing the relevance of experimental findings to human disease, HSF1 was activated in the stroma of a wide variety of human cancers, and this activation correlated strongly with poor outcome in both lung and breast cancer. For therapy implication, targeting normal biological networks that have been co-opted to support malignancy create a new way for cancer therapy, rather than relying solely on the targeting of mutated malignant drivers.


1. Bissell, M.J., and Hines, W.C. (2011). Why don’t we get more cancer? A pro-posed role of the microenvironment in restraining cancer progression. Nat. Med. 17, 320–329.

2. Kojima, Y., Weinberg, R.A., and Orimo, A. et al. (2010). Autocrine TGF-beta and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts. Proc. Natl. Acad. Sci. USA 107, 20009–20014.