Asparagine, colorectal cancer, and the role of sex, genes, microbes, and diet: A narrative review

Authors

Xinyi Shen, Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, United States.Follow
Abhishek Jain, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, United States.Follow
Oladimeji Aladelokun, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, United States.Follow
Hong Yan, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, United States.Follow
Austin Gilbride, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, United States.
Leah M. Ferrucci, Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, United States.
Lingeng Lu, Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, United States.Follow
Sajid A. Khan, Division of Surgical Oncology, Department of Surgery, Yale University School of Medicine, New Haven, CT, United States.Follow
Caroline H. Johnson, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, United States.Follow

Document Type

Article

Publication Title

Frontiers in molecular biosciences

Abstract

Asparagine (Asn) and enzymes that catalyze the metabolism of Asn have been linked to the regulation and propagation of colorectal cancer (CRC). Increased Asn and asparagine synthetase (ASNS) expression, both contribute to CRC progression and metastasis. In contradistinction, L-asparaginase (ASNase) which breaks down Asn, exhibits an anti-tumor effect. Metabolic pathways such as KRAS/PI3K/AKT/mTORC1 signaling and high SOX12 expression can positively regulate endogenous Asn production. Conversely, the tumor suppressor, TP53, negatively impacts ASNS, thus limiting Asn synthesis and reducing tumor burden. Asn abundance can be altered by factors extrinsic to the cancer cell such as diet, the microbiome, and therapeutic use of ASNase. Recent studies have shown that sex-related factors can also influence the regulation of Asn, and high Asn production results in poorer prognosis for female CRC patients but not males. In this narrative review, we critically review studies that have examined endogenous and exogenous modulators of Asn bioavailability and summarize the key metabolic networks that regulate Asn metabolism. We also provide new hypotheses regarding sex-related influences on Asn, including the involvement of the sex-steroid hormone estrogen and estrogen receptors. Further, we hypothesize that sex-specific factors that influence Asn metabolism can influence clinical outcomes in CRC patients.

First Page

958666

DOI

10.3389/fmolb.2022.958666

Publication Date

1-1-2022

Recommended Citation

Shen, Xinyi; Jain, Abhishek; Aladelokun, Oladimeji; Yan, Hong; Gilbride, Austin; Ferrucci, Leah M.; Lu, Lingeng; Khan, Sajid A.; and Johnson, Caroline H., "Asparagine, colorectal cancer, and the role of sex, genes, microbes, and diet: A narrative review" (2022). Surgery. 184.
https://scholar.bridgeporthospital.org/surgery/184

Identifier

36090030 (pubmed); PMC9453556 (pmc); 10.3389/fmolb.2022.958666 (doi); 958666 (pii)