Occurrence of Differing Metabolic Dysregulations, a Glucose Driven and Another Fatty Acid Centric in Gastric Cancer Subtypes

Overview

Journal Funct Integr Genomics

Publisher Springer

Specialties Genetics
Molecular Biology

Date 2020 Sep 19

PMID 32949316

Citations 5

Authors

Karthik Balakrishnan

Kumaresan Ganesan

Affiliations

Soon will be listed here.

Abstract

Gastric cancer is one of the most common cancers and ranks third in cancer-related deaths across globe. Cancer cells are known to take advantage of the altered metabolic processes to sustain their survival, proliferation, and cancer progression. In this investigation, we explored the available genome-wide expression profiles of few hundreds of gastric tumors and non-cancerous gastric tissues and analyzed in the context of metabolic pathways. Gastric tumors were investigated for the metabolic processes related to glucose metabolism, glucose transport, glutamine metabolism, and fatty acid metabolism, by metabolic pathway-focused gene set enrichment analysis. Notably, all glucose metabolism and glutamine metabolism-related gene sets were found enriched in intestinal subtype gastric tumors. On the other hand, the gene sets related to glucose transport and glucan (glycan) metabolisms are enriched in diffuse subtype gastric tumors. Strikingly, fatty acid metabolisms, fatty acid transport, and fat differentiation-related signatures are also highly activated in diffuse subtype gastric tumors. Exploration of the recently established metabolome profile of the massive panel of cell lines also revealed the metabolites of glucose and fatty acid metabolic pathways to show the differing abundance across gastric cancer subtypes. The subtype-specific metabolic rewiring and the existence of two distinct metabolic dysregulations involving glucose and fatty acid metabolism in gastric cancer subtypes have been identified. The identified differing metabolic dysregulations would pave way for the development of targeted therapeutic strategies for the gastric cancer subtypes.

Citing Articles

Investigating the dysregulation of genes associated with glucose and lipid metabolism in gastric cancer and their influence on immunity and prognosis.

Li Y, Zeng Z Biofactors. 2024; 51(1):e2138.

PMID: 39508713 PMC: 11681298. DOI: 10.1002/biof.2138.

Amplification of Hippo Signaling Pathway Genes Is Governed and Implicated in the Serous Subtype-Specific Ovarian Carcino-Genesis.

Balakrishnan K, Chen Y, Dong J Cancers (Basel). 2024; 16(9).

PMID: 38730733 PMC: 11082992. DOI: 10.3390/cancers16091781.

Classification of stomach adenocarcinoma based on fatty acid metabolism-related genes frofiling.

Liu C, Tao Y, Lin H, Lou X, Wu S, Chen L Front Mol Biosci. 2022; 9:962435.

PMID: 36090054 PMC: 9461144. DOI: 10.3389/fmolb.2022.962435.

The Role of Lipid Metabolism in Gastric Cancer.

Cui M, Yi X, Zhu D, Wu J Front Oncol. 2022; 12:916661.

PMID: 35785165 PMC: 9240397. DOI: 10.3389/fonc.2022.916661.

Metabolic Reprogramming in Gastric Cancer: Trojan Horse Effect.

Bin Y, Hu H, Tian F, Wen Z, Yang M, Wu B Front Oncol. 2022; 11:745209.

PMID: 35096565 PMC: 8790521. DOI: 10.3389/fonc.2021.745209.

References

Alo P, Visca P, Botti C, Galati G, Sebastiani V, Andreano T . Immunohistochemical expression of human erythrocyte glucose transporter and fatty acid synthase in infiltrating breast carcinomas and adjacent typical/atypical hyperplastic or normal breast tissue. Am J Clin Pathol. 2001; 116(1):129-34. DOI: 10.1309/5Y2L-CDCK-YB55-KDK6. View

Anderson N, Mucka P, Kern J, Feng H . The emerging role and targetability of the TCA cycle in cancer metabolism. Protein Cell. 2017; 9(2):216-237. PMC: 5818369. DOI: 10.1007/s13238-017-0451-1. View

Baenke F, Peck B, Miess H, Schulze A . Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development. Dis Model Mech. 2013; 6(6):1353-63. PMC: 3820259. DOI: 10.1242/dmm.011338. View

Barrett T, Wilhite S, Ledoux P, Evangelista C, Kim I, Tomashevsky M . NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res. 2012; 41(Database issue):D991-5. PMC: 3531084. DOI: 10.1093/nar/gks1193. View

Biswas S, Lunec J, Bartlett K . Non-glucose metabolism in cancer cells--is it all in the fat?. Cancer Metastasis Rev. 2012; 31(3-4):689-98. DOI: 10.1007/s10555-012-9384-6. View

Cheadle C, Vawter M, Freed W, Becker K . Analysis of microarray data using Z score transformation. J Mol Diagn. 2003; 5(2):73-81. PMC: 1907322. DOI: 10.1016/S1525-1578(10)60455-2. View

Currie E, Schulze A, Zechner R, Walther T, Farese Jr R . Cellular fatty acid metabolism and cancer. Cell Metab. 2013; 18(2):153-61. PMC: 3742569. DOI: 10.1016/j.cmet.2013.05.017. View

Daniels V, Smans K, Royaux I, Chypre M, Swinnen J, Zaidi N . Cancer cells differentially activate and thrive on de novo lipid synthesis pathways in a low-lipid environment. PLoS One. 2014; 9(9):e106913. PMC: 4162556. DOI: 10.1371/journal.pone.0106913. View

Epstein T, Gatenby R, Brown J . The Warburg effect as an adaptation of cancer cells to rapid fluctuations in energy demand. PLoS One. 2017; 12(9):e0185085. PMC: 5602667. DOI: 10.1371/journal.pone.0185085. View

10.

Favaro E, Bensaad K, Chong M, Tennant D, Ferguson D, Snell C . Glucose utilization via glycogen phosphorylase sustains proliferation and prevents premature senescence in cancer cells. Cell Metab. 2012; 16(6):751-64. DOI: 10.1016/j.cmet.2012.10.017. View

11.

Fischer G, Gopal Y, McQuade J, Peng W, DeBerardinis R, Davies M . Metabolic strategies of melanoma cells: Mechanisms, interactions with the tumor microenvironment, and therapeutic implications. Pigment Cell Melanoma Res. 2017; 31(1):11-30. PMC: 5742019. DOI: 10.1111/pcmr.12661. View

12.

Fouad Y, Aanei C . Revisiting the hallmarks of cancer. Am J Cancer Res. 2017; 7(5):1016-1036. PMC: 5446472. View

13.

Freedman J, Tyler D, Nevins J, Augustine C . Use of gene expression and pathway signatures to characterize the complexity of human melanoma. Am J Pathol. 2011; 178(6):2513-22. PMC: 3124358. DOI: 10.1016/j.ajpath.2011.02.037. View

14.

Furuta E, Pai S, Zhan R, Bandyopadhyay S, Watabe M, Mo Y . Fatty acid synthase gene is up-regulated by hypoxia via activation of Akt and sterol regulatory element binding protein-1. Cancer Res. 2008; 68(4):1003-11. DOI: 10.1158/0008-5472.CAN-07-2489. View

15.

Hochachka P, Rupert J, Goldenberg L, Gleave M, Kozlowski P . Going malignant: the hypoxia-cancer connection in the prostate. Bioessays. 2002; 24(8):749-57. DOI: 10.1002/bies.10131. View

16.

Hur H, Paik M, Xuan Y, Nguyen D, Ham I, Yun J . Quantitative measurement of organic acids in tissues from gastric cancer patients indicates increased glucose metabolism in gastric cancer. PLoS One. 2014; 9(6):e98581. PMC: 4049586. DOI: 10.1371/journal.pone.0098581. View

17.

LAUREN P . THE TWO HISTOLOGICAL MAIN TYPES OF GASTRIC CARCINOMA: DIFFUSE AND SO-CALLED INTESTINAL-TYPE CARCINOMA. AN ATTEMPT AT A HISTO-CLINICAL CLASSIFICATION. Acta Pathol Microbiol Scand. 1965; 64:31-49. DOI: 10.1111/apm.1965.64.1.31. View

18.

Lee W, Guo P, Lim S, Bassilian S, Lee S, Boren J . Metabolic sensitivity of pancreatic tumour cell apoptosis to glycogen phosphorylase inhibitor treatment. Br J Cancer. 2004; 91(12):2094-100. PMC: 2409791. DOI: 10.1038/sj.bjc.6602243. View

19.

Lee S, Bae S, Park Y, Park J, Kim T, Yoon H . Correlation of Molecular Subtypes of Invasive Ductal Carcinoma of Breast with Glucose Metabolism in FDG PET/CT: Based on the Recommendations of the St. Gallen Consensus Meeting 2013. Nucl Med Mol Imaging. 2017; 51(1):79-85. PMC: 5313467. DOI: 10.1007/s13139-016-0444-7. View

20.

Levine A, Puzio-Kuter A . The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science. 2010; 330(6009):1340-4. DOI: 10.1126/science.1193494. View