PITTSBURGH (Apr. 9,
2021) … University of Pittsburgh bioengineer Partha Roy received awards from
Cancer Institute (NCI) of the National Institute of Heath and the Magee
Women’s Cancer Research and Education Funding Committee to investigate the role
of actin-binding protein profilin1 in metastatic breast cancer -- the second
most common cancer among women in the United States. In 2021,
an estimated 281,550 new cases of invasive breast cancer will be diagnosed in
U.S. women, and around 15 percent of those cases are expected to be fatal.
“Metastatic cancer is the cause of the majority of breast
cancer deaths,” said Roy, who leads the Cell Migration Lab at Pitt’s Swanson
School of Engineering. “During metastasis, nests of cells escape from the
primary tumor and spread to other parts of the body. Treating these metastatic
growths only temporizes the lethal outcome, so my group will investigate the
mechanism that leads to metastatic dissemination and growth.”
Roy’s lab previously found that profilin1 has contrasting
effects on early vs. late stage of breast cancer metastasis. While reduced
level of profilin1 in cancer cells makes these cells more migratory and
competent in dissemination from the primary tumor, cancer cells are dependent
on profilin1’s action for metastatic colonization.
As part of the NCI-R01 grant, Roy’s lab will study how
profilin1 controls lipid signaling and the downstream processes during
dissemination of breast cancer cells. This study will be in collaboration with
Pitt’s Gerry Hammond, assistant professor of cell biology, and Beth Roman, associate
professor of human genetics and member of the Vascular Medicine Institute.
The pilot grant from the Magee Women’s Cancer Research will have
two foci. They will conduct preclinical proof-of-concept studies to
determine whether novel small molecules targeting the profilin1-actin
interaction suppress metastatic colonization of breast cancer cells. They will
also examine the mechanistic understanding of how profilin1’s interaction with
actin activates certain signaling pathways to regulate dormancy-to-emergence
behavior of cancer cells.
These studies could pave the way for novel therapeutic
directions in metastatic breast cancer.
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and X-Ray images demonstrating that knockdown (KD) of profilin1 (Pfn1)
expression dramatically suppresses metastatic colonization ability of breast
cancer cells in mouse model
Contact: Leah Russell