HSF-1 Can Transform Stromal Cells to Promote Malignant Progression

Long associated with enabling the proliferation of cancer cells, the ancient cellular survival response regulated by Heat-Shock Factor 1 (HSF1) can also turn neighboring cells in their environment into co-conspirators that support malignant progression and metastasis.

The finding, reported by Whitehead Institute scientists this week in the journal Cell, lends new insights into tumor biology with significant implications for the diagnosis, prognosis, and management of cancer patients.

Over the past several years, researchers in the lab of Whitehead Member Susan Lindquist have been investigating the role the transcription factor HSF1 plays in supporting malignancy. In normal cells, stressful conditions, including those caused by heat, hypoxia, and toxins activate HSF1, which serves to maintain protein homeostasis and helps the cells endure tough times. Cancer cells, however, are capable of hijacking this heat-shock response to their own benefit. Two years ago, Lindquist’s lab implicated HSF1 in this corruption, showing that it activates a set of genes in cancer cells quite distinct from those up-regulated in normal cells during heat-shock.

Building upon that research, the lab has now discovered that HSF1 operates not only on the cancer cells in a tumor, but also on the cells of the tumor microenvironment, or stroma. Here HSF1 drives a transcriptional program distinct from that operating in adjacent cancer cells. HSF1 activation in both cancer cells and stromal cells is a powerful, complementary combination that fuels malignant processes.

Press release: http://bit.ly/1n7paF4

Source: Whitehead Institute