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The important role of HSF1 expressed by cancer-associated fibroblasts

 

Tumor cells are surrounded by stromal cells, including fibroblasts etc., and extracellular matrix (ECM), which are called tumor microenvironment and are important for tumor development, progression and metastasis. Scherz-Shouval et al. found cancer-associated fibroblasts (CAFs) frequently express heat shock factor 1 (HSF1), which acts as a strong enabler of tumorigenesis. The article was published on Cell.

 

HSF1 is a transcription factor expressed ubiquitously that is usually activated by heat. However, it has been shown to be activated in a different manner in cancer cells, and play a key role in tumorigenesis. It interferences apoptotic responses and facilitates signaling pathways associated with cell metabolism, proliferation, invasion, and metastasis. Researchers found HSF1 is highly expressed in CAFs, which is the most abundant cells within tumor micorenvironment. In CAFs, HSF1 drives the secretion of factors that promote tumor cell survival and proliferation in a  non-cell-autonomous manner, which is different from the cell-autonomous program it induces in adjacent cancer cells. In addition, researchers demonstrated transforming growth factor β (TGF-β) and stromal cell-derived factor 1 (SDF1) are two critical signaling molecules in regulation of non-cell-autonomous program in CAFs. The findings indicate HSF1 supports malignancy in both non-cell-autonomous cell-autonomous ways in tumor microenvironment.

 

Reference:
Cell. 2014 Jul 31;158(3):564-78. 

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