The journal Oncogene published new work by University of Illinois Cancer Center members David Crowe, DDS, PhD, and Jianchun Wu, MD, PhD, and co-author Kaitrin Kramer, DDS, PhD, MS, formerly of the University of Illinois Chicago (UIC) and now a craniofacial orthodontist at Nationwide Children’s Hospital in Columbus, Ohio.
In the study, “Lysine metabolism is a novel metabolic tumor suppressor pathway in breast cancer,” the three note that the International Agency for Research on Cancer called obesity the main preventable cause of breast cancer.
“We created a new model to better understand how the obese microenvironment alters nuclear receptor function in breast cancer,” they wrote.
Crowe and Wu are part of the Cancer Center’s Cancer Biology research program. Crowe is a Professor of Periodontics at the University of Illinois Chicago College of Dentistry and Wu is a Research Associate Professor of Periodontics there.
From Oncogene
Here is an excerpt from their study abstract. Read the full study here.
“The nuclear receptor peroxisome proliferator activated receptor γ (PPARγ) binds inflammatory mediators in obesity and its expression is reduced in human breast cancer. … The obesity related cancer phenotype was PPARγ dependent; deletion of PPARγ in mammary epithelium which is a tumor suppressor in lean mice unexpectedly increased tumor latency, reduced the luminal progenitor (LP) tumor cell fraction, and increased autophagic and senescent cells. Loss of PPARγ expression in mammary epithelium of obese mice increased expression of 2-aminoadipate semialdehyde synthase (AASS) which regulates lysine catabolism to acetoacetate. PPARγ-associated co-repressors and activators regulated AASS expression via a canonical response element. AASS expression was significantly reduced in human breast cancer, and AASS overexpression or acetoacetate treatment inhibited proliferation and induced autophagy and senescence in human breast cancer cell lines. Genetic or pharmacologic HDAC inhibition promoted autophagy and senescence in mammary tumor cells in vitro and in vivo. We concluded that lysine metabolism is a novel metabolic tumor suppressor pathway in breast cancer.”