A recent study by the Georgia Health Sciences University has shed light on the previously unconfirmed association of Hsf1 with cancer activity. The researchers have demonstrated the effect of Hsf1 on tumourigenesis and metastasis of ErbB2-induced breast cancer.  It seems that deletion of Hsf1 in mice carrying Her2/Neu significantly reduces the activity associated with breast cancer and metastasis by reducing ERK1/2 activity and the epithelial-mesenchymal transition (EMT) of mammary epithelial cells.

Hsf1 is a key regulator for cellular release of heat shock proteins (Hsp70, Hsp27, Hsp90 etc).  These proteins are responsible for ensuring proper protein folding and many have been linked to cancer activity.  EMT is an occurrence where epithelial cells are influenced to become mesenchymal cells; an aberration that leads to cancer.  EMT is a critical step for metastasis; where the cancer leaves the original site with the attributes necessary for spreading the cancer to other tissues.

ErbB2/Her2/Neu receptors are known oncogenes that have been shown to be present in some breast cancers, promoting invasion and metastasis.  When this complex associates with Her3 or Her4, it activates MAPK and PI3K/AKT signalling pathways, leading to further cellular proliferation, increased motility and inhibition of apoptosis.  These changes are associated with cancer development.

Further, these researchers have determined that “Hsf1 protects mammary epithelial cells from apoptosis and increases their proliferative capacity” – another way in which Hsf1 promotes cancer.  They have also shown that mammary gland morphogenesis is promoted by Hsf1.  Angiogenesis also seems to be potentiated by Hsf1.

Taken together, it seems that Hsf1 is a major player in breast cancer’s hijacking of cellular machinery – at multiple points and to develop and spread.  Eliminating Hsf1 altogether in cancer patients may cause more harm than good, but this new understanding of the relationships at play should allow for more downstream products of Hsf1 to be investigated as targets for cancer therapy.

The original research paper was published in: The Journal of Biological Chemistry, July 2012

Heat Shock Factor Hsf1 Cooperates with ErbB2 (Her2/Neu) Protein to Promote Mammary Tumourigenesis and Metastasis.

In this study, StressMarq monoclonal Hsp90alpha antibody (product# SMC-108) was used in immunoblotting to determine changes in levels of the protein.