A new review by University of California, Irvine researchers at the School of Pharmacy & Pharmaceutical Sciences (SPPS) describes the molecular process by which Wnt protein signaling intersects with metabolic networks to promote tissue growth and remodeling in metabolic and endocrine disorders. Wnt signaling is a central mechanism during development that enables rapid cell growth. Cancer cells hijack the Wnt signaling mechanism to promote rapid proliferation and expansion of tumors. While the Wnt signaling pathway has been well described in cancer, this process is also misregulated in disorders stemming from the endocrine system. However, because of our lack of molecular mechanistic knowledge, it is difficult to target Wnt signaling via therapeutic approaches. Hence, the title of the current report “Metabolism and Endocrine Disorders: What Wnt Wrong?”.
“The role of metabolism is a vital function in living organisms. Our study describes the molecular process of Wnt signaling, a central mechanism during development that enables rapid cell growth. Cancer cells hijack that mechanism to promote rapid proliferation and expansion of tumors. These findings help address the gaps in our knowledge of the regulation of Wnt signaling and help identify new therapeutic targets for diseases such as cancer and endocrine disorders,” says Lauren Albrecht, assistant professor of pharmaceutical sciences and corresponding author.
The team describes how Wnt signaling is implicated in the regulation of metabolism at the cellular level and recent work demonstrates that Wnt signaling finds a new purpose for the lysosome protein degradation system. The cellular organelle lysosome functions as the digestive system of the cell, breaking down material taken in from outside and digesting obsolete components of the cell itself. Wnt signaling repurposes the lysosome’s degradation system. A key driver of these processes is regulated by a chemical modification known as methylation, which operates as a light switch to turn signaling on or off.
The team revealed a new function of methylation, in which it serves as a shipping label and tags specific proteins to be broken down. “These findings provide key insights into understanding the cellular processes that regulate Wnt signaling, which will help advance the development of therapeutics for cancer and other endocrine disorders and also identify biomarkers of disease progression,” says Lauren Albrecht, pharmaceutical sciences assistant professor and corresponding author. The research team also included pharmaceutical sciences students Carolina Franco (PhD program) and senior May Myat Noe. The review is published in the online journal Frontiers in Endocrinology.