Download Sepideh Vahid

Name of Student:
Sepideh Vahid
Research Supervisor:
Dr. Amina Zoubeidi
HSP 27 INTERACTS WITH THE HIPPO PATHWAY TO
REGULATE CELL SURVIVAL IN CANCER.
Title of Presentation:
Abstract
Heat shock protein 27 (Hsp27) is a molecular chaperone highly and uniformly expressed in
treatment resistant cancers like castrate resistant prostate cancer (CRPC). Hsp27 regulates
activity of several oncogenic pathways and its levels correlate with aggressive tumor
behaviour, drug resistance and tumor growth. Similarly, dysregulation of the Hippo tumor
suppressor pathway, which restricts organ size and cell proliferation, occurs in many types of
cancers. In healthy cells, activation of the Hippo pathway results in phosphorylation and
cytoplasmic retention of two transcriptional co-activators YAP and TAZ, whereas in cancer
YAP and TAZ are free to translocate to the nucleus and increase cell proliferation by
promoting the activities of certain transcriptional factors.
Our preliminary findings indicate that Hsp27 negatively affects the Hippo pathway. We have
found that targeting Hsp27 using siRNA in the prostate cancer cell line PC-3 leads to increased
cytoplasmic retention of p-YAP compared to control siRNA treated cells. Moreover, using
immunofluorescence, we observed reduced nuclear translocation of the YAP/TAZ as well as
sequestration of these components with cytoplasmic 14-3-3 proteins in siRNA treated PC3
cells.
Future studies will be directed at Hsp27 gain and loss of function experiments as well as
identifying YAP/TAZ expression in human prostate cancer specimens.
Impact: Our data supports the significance of targeting Hsp27 as a treatment option in cancers,
especially metastatic malignancies like CRPC.