Glucose metabolic reprogramming and cell proliferation arrest in colorectal micropapillary carcinoma Journal Article
| Authors: | Vyas, M.; Patel, N.; Celli, R.; Wajapeyee, N.; Jain, D.; Zhang, X. |
| Article Title: | Glucose metabolic reprogramming and cell proliferation arrest in colorectal micropapillary carcinoma |
| Abstract: | Background: Micropapillary carcinoma (MPC) has been reported as an aggressive variant of colorectal carcinoma (CRC) associated with frequent lymphovascular invasion and poor outcome. Altered glycogen metabolism by metabolic reprogramming plays a critical role for cancer cell growth and survival. We aimed to investigate glucose metabolic reprogramming in colorectal MPC. Methods: Immmunostains for Ki-67 and glucose transporter 1 (GLUT1) were performed on 10 colorectal MPCs. Real-time PCR analysis of expressions of GLUT] and glycogen metabolizing enzymes: glycogen synthase (GYS1) and glycogen phosphorylase (PYGL) was perfonned on cultured monolayer and three-dimensional (3D) spheroid HCT116 colon cancer cells. Results: GLUT I was strongly expressed in MPC as compared to adjacent conventional glandular component, and was also significantly increased expression in 3D spheroids. Upregulation of GYS1 and PYGL was markedly increased in 3D spheroids. The proliferation rate (Ki-67) of MPC was significantly lower compared to conventional glandular component. The 3D spheroids showed increased cell cycle arrest. Our results demonstrate altered glycogen metabolism in colorectal MPC. Conclusion: The reprogramming of glycogen metabolism in MPC provides a source of energy contributing to tumor cell survival in a low proliferation state. Targeting glucose-regulated metabolism may warrant consideration as possible MPC therapies. |
| Keywords: | survival; metabolism; colorectal carcinoma; hypoxia; glucose; colon; micropapillary carcinoma; expression; component; poor-prognosis; subtype; lymph-node metastasis; glycogen-metabolism; tnm stages i |
| Journal Title: | Gastroenterology Research |
| Volume: | 12 |
| Issue: | 3 |
| ISSN: | 1918-2805 |
| Publisher: | Elmer Press Inc |
| Date Published: | 2019-06-01 |
| Start Page: | 128 |
| End Page: | 134 |
| Language: | English |
| ACCESSION: | WOS:000473279500004 |
| DOI: | 10.14740/gr1145 |
| PROVIDER: | wos |
| PMCID: | PMC6575135 |
| PUBMED: | 31236153 |
| Notes: | Article -- Source: Wos |
