New! Sign up for our free email newsletter.
Science News
from research organizations

Targeting enzyme could alleviate muscle wasting for cancer patients

Date:
October 17, 2022
Source:
University of Texas Health Science Center at Houston
Summary:
Targeting a specific enzyme in the muscle could help cancer patients preserve muscle mass and potentially prolong their survival, according to new research.
Share:
FULL STORY

Targeting a specific enzyme in the muscle could help cancer patients preserve muscle mass and potentially prolong their survival, according to research from UTHealth Houston.

A study led by Yi-Ping Li, PhD, professor in the Department of Integrative Biology and Pharmacology with McGovern Medical School at UTHealth Houston, found that an enzyme known as UBR2 plays a critical role in cancer-induced muscle wasting, also called cancer cachexia.

The results were published today in the scientific journal PNAS.

"The findings will fill a key gap in understanding how cancer causes muscle mass and function loss," said Li, senior author of the study and a faculty member with The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences.

Cancer cachexia is a complication developed in the late stages of cancer in roughly 60% of all cancer patients. Cachexia patients waste away by losing body weight, primarily due to progressive loss of muscle mass, causing respiratory and heart failure. Approximately 30% of all cancer patients die of cachexia, making the complication a major determinant of cancer survival.

Historically, there has been no treatment of cancer cachexia due to poor understanding of its origins. Therefore, a key focus of Li's lab over the past two decades has been to decipher the molecular mechanisms through which cancer causes cachexia.

Building upon a series of discoveries in mice, his lab recently identified the role of the enzyme UBR2. This is the key enzyme in muscle that seeks out subtypes of the contractile protein myosin heavy chain, a critical component for sustaining muscle contraction, for destruction in response to cancer.

Cancer causes an increase of UBR2 in muscle, and blocking the increase of or removing UBR2 spares mice from tumor-caused muscle mass and function loss. By examining the muscle of cancer patients, researchers obtained evidence that UBR2 is increased, which is associated with loss of the specific subtype of myosin heavy chain preferentially lost in cachexia.

Li said this discovery is significant for the future of cancer cachexia therapy.

"We have learned in animal studies that muscle wasting in cancer hosts can be ameliorated by blocking UBR2 increase through repurposing some existing drugs," he said. "Based on the findings, we plan to conduct clinical trials for the therapy of cancer cachexia."

Song Gao, PhD, former postdoctoral research fellow with McGovern Medical School, was the first author of the study. Co-authors with the Department of Integrative Biology and Pharmacology at McGovern Medical School included Yong Zhou, PhD, assistant professor, as well as former faculty members Guohua Zhang, PhD; Zicheng Zhang, MD, PhD; James Z. Zhu; and Li Li, PhD.

Other co-authors were George G. Rodney Jr., PhD, and Reem S. Abo-Zahrah, PhD, both with Baylor College of Medicine in Houston; Lindsey Anderson, PhD, and Jose M. Garcia, MD, PhD, both with VA Puget Sound Health Care System in Seattle; and Yong Tae Kwon, PhD, with Seoul National University in South Korea.


Story Source:

Materials provided by University of Texas Health Science Center at Houston. Original written by Caitie Barkley. Note: Content may be edited for style and length.


Journal Reference:

  1. Song Gao, Guohua Zhang, Zicheng Zhang, James Z. Zhu, Li Li, Yong Zhou, George G. Rodney, Reem S. Abo-Zahrah, Lindsey Anderson, Jose M. Garcia, Yong Tae Kwon, Yi-Ping Li. UBR2 targets myosin heavy chain IIb and IIx for degradation: Molecular mechanism essential for cancer-induced muscle wasting. Proceedings of the National Academy of Sciences, 2022; 119 (43) DOI: 10.1073/pnas.2200215119

Cite This Page:

University of Texas Health Science Center at Houston. "Targeting enzyme could alleviate muscle wasting for cancer patients." ScienceDaily. ScienceDaily, 17 October 2022. <www.sciencedaily.com/releases/2022/10/221017161116.htm>.
University of Texas Health Science Center at Houston. (2022, October 17). Targeting enzyme could alleviate muscle wasting for cancer patients. ScienceDaily. Retrieved April 15, 2024 from www.sciencedaily.com/releases/2022/10/221017161116.htm
University of Texas Health Science Center at Houston. "Targeting enzyme could alleviate muscle wasting for cancer patients." ScienceDaily. www.sciencedaily.com/releases/2022/10/221017161116.htm (accessed April 15, 2024).

Explore More

from ScienceDaily

RELATED STORIES