Massey researcher awarded $1.1M to study the role of fatty acids in the development of breast cancer
VCU Massey Cancer Center researcher Xianjun Fang, M.S., Ph.D., was awarded more than $1.1 million by the U.S. Department of Defense to study how an enzyme that plays a role in metabolizing fatty acids contributes to the development of breast cancer. He hopes this research will translate into the creation of novel therapies.
Obesity is a well-known risk factor for breast cancer, and rapidly dividing tumor cells depend on their own ability to produce fats, or lipids, to continue building more cells.
Recent research has suggested that cancer cells demonstrate an enhanced ability to consume fats and provide energy to malignant cells through a process called fatty acid oxidation (FAO), a function that could directly explain the link between obesity and increased risk and mortality of breast cancer.
FAO is directly controlled by a rate-limiting enzyme called carnitine palmitoyltransferase 1A (CPT1A).
Through preliminary studies, Fang has found that the CPT1A protein is abundant in breast cancer cell lines (including ER-positive, triple-negative and primary invasive ductal carcinomas) and its overexpression is strongly associated with poor survival in breast cancer patients.
The inactivation of CPT1A was shown to suppress cell growth and reduce energy production, suggesting that breast cancer cells rely significantly on FAO to grow and multiply.
Fang’s continuing research, funded by the U.S. Army in the amount of $1,143,750 through 2020, will examine whether FAO is required for breast cancer development and explore the therapeutic benefits of inhibiting CPT1A and other FAO blockers in breast cancer models.
“Fatty acid oxidation is poorly studied in the context of cancer. This project will add a new metabolic process to the current snapshot of metabolic transformation in cancer. In addition to potentially providing a mechanistic link between obesity and high risk and poor prognosis of breast cancer, the results may also lead to the development and validation of anti-FAO approaches to treating breast cancer,” said Fang, a member of the Cancer Cell Signaling research program at Massey and associate professor of biochemistry and molecular biology at the VCU School of Medicine.
In addition, preliminary research by Fang identified CPT1A in the maintenance of cancer stem cells, which are responsible for cancer growth, metastasis, recurrence and resistance to chemotherapy andradiation therapy. The inhibition of CPT1A prevented cancer stem cells from escapingchemotherapeutic drugs. Fang theorizes that CPT1A is a primary actor in breast cancer development and metastasis.
“Intervention of CPT1A could have profound effects on the malignant features of breast cancer. My laband collaborators are very excited to receive this highly competitive grant funding from the U.S Department of Defense to start a different avenue of breast cancer research,” Fang said.
This grant (W81XWH1710317) was awarded by the U.S. Army's Office of Medical Research & Material Command/Congressionally Directed Medical Research Programs.
Fang is collaborating on this research with Dipankar Bandyopdhyay, Ph.D., member of the Cancer Prevention and Control research program at Massey, and Michael Idowu, M.D., M.P.H., the director of breast pathology at VCU.