Markey study identifies new target for obesity-related breast cancer
University of Kentucky Markey Cancer Center researchers have identified a protein that could be a promising treatment target for obesity-related breast cancer.
The study, published in Breast Cancer Research, shows that a protein called Hsp47 becomes more active in fat tissue during obesity and helps cancer tumors grow by changing the surrounding tissue environment.
“The findings could eventually lead to new treatments for breast cancer as well as those that target the obesity-cancer connection in humans,” says Ren Xu, Ph.D., the study’s senior author and professor in the UK College of Medicine’s Department of Pharmacology and Nutritional Sciences.
Xu’s study showed that Hsp47 works through another protein called asporin. In healthy conditions, both proteins remain at normal levels. During obesity, however, Hsp47 increases and helps pump out more asporin, which stiffens the tissue matrix around tumors and makes it easier for cancer to grow.
His team tested their findings using a drug called Col003 that blocks Hsp47 activity. Mice on high-fat diets that were treated with the compound showed reduced weight gain and slower tumor growth compared to those that were untreated.
The study also found that blocking Hsp47 increased the number of immune cells called T-cells around tumors. These cells normally fight cancer, but obesity often suppresses their activity. By removing the protein’s influence, the researchers restored some of the immune system’s natural cancer-fighting ability.
Obesity remains a significant health challenge in the U.S., particularly in Kentucky. Approximately 48% of Kentuckians are classified as obese. Previous studies have linked excess weight to an increased risk of cancer and poorer outcomes for various cancer types, including breast cancer. The new findings help explain this connection at the molecular level and have identified a potential target to inhibit obesity-associated cancer progression.
The research builds on Xu’s previous work that identified Hsp47 as playing a role in breast cancer metastasis. In 2020, his team showed the protein helps cancer cells spread to distant organs by strengthening their interactions with blood platelets.
Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under Award Number R21AG080176, and the National Cancer Institute of the National Institutes of Health under Award Numbers R01CA207772, R01CA277946, R01CA274981 and R01CA211695. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
