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J Med Oncl Ther 2017 | Volume 2 Issue 4
Oncology and Biomarkers Summit
November 27-28, 2017 | Atlanta, USA
Annual Congress on
GDF15, potential mediator of resistance and disease progression in breast cancer
Rita Nahta
Emory University, USA
Statement of the Problem:
Breast cancer-related deaths are due
primarily to drug-resistant, metastatic disease. Identification of
molecularmechanismsmediatingresistanceandinvasionwillallow
new targeted therapies to be developed. Growth differentiation
factor 15 (GDF15) is an inflammatory cytokine overexpressed in
many types of solid tumors, including breast. Past studies have
linkedhighGDF15 levelswithHER2overexpression, drugresistance
and cancer stemcell-like characteristics.
Methods:
By IHC and informatics, we examined GDF15 in
breast tumor tissues and correlated with clinical characteristics
or outcomes. Using 2-d and 3-d cellular assays, we examined
the role of GDF15 in breast cancer cell proliferation, epithelial
mesenchymal transition (EMT), spheroid growth and
invasion. Molecular studies, including genetic knockdown
and pharmacological inhibition paired with western blotting
and PCR, examined the mechanisms through which GDF15
promoted breast cancer cell invasion.
Findings:
High GDF15 is associated with high tumor grade,
ER-negative status and HER2 overexpression. Stable GDF15
transfection induces EMT and invasion. Upregulation of
transcription factor FoxM1 with subsequent induction
of target matrix metalloproteinases (MMPs) is required
for GDF15-mediated effects, as FoxM1 knockdown and
MMP inhibition rescues invasion and EMT. Further, GDF15
knockdown or pharmacological blockade significantly
inhibits invasion of HER2-overexpressing and triple-negative
breast cancer cells.
Conclusion & Significance:
These findings support further
preclinical investigation of the role of GDF15 in breast cancer
progression and development of GDF15-targeted therapies
for breast cancer treatment.
Speaker Biography
Rita Nahta is an expert in breast cancer pharmacology. She has published extensively
on mechanisms of resistance to targeted therapies in breast cancer, with a focus on
kinase signaling cross talk and novel combination approaches to treating drug-resistant
breast cancer.
e:
Rnahta@emory.edu