| Autor: |
Vasconcelos-Dos-Santos A; Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brazil., Loponte HF; Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brazil., Mantuano NR; Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brazil., Oliveira IA; Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brazil., de Paula IF; Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Teixeira LK; Programa de Biologia Celular, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil., de-Freitas-Junior JC; Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Gondim KC; Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Heise N; Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brazil., Mohana-Borges R; Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brazil., Morgado-Díaz JA; Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Dias WB; Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brazil., Todeschini AR; Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brazil. |
| Abstrakt: |
Hyperglycemia is a common feature of diabetes mellitus, considered as a risk factor for cancer. However, its direct effects in cancer cell behavior are relatively unexplored. Herein we show that high glucose concentration induces aberrant glycosylation, increased cell proliferation, invasion and tumor progression of colon cancer. By modulating the activity of the rate-limiting enzyme, glutamine-fructose-6-phosphate amidotransferase (GFAT), we demonstrate that hexosamine biosynthetic pathway (HBP) is involved in those processes. Biopsies from patients with colon carcinoma show increased levels of GFAT and consequently aberrant glycans' expression suggesting an increase of HBP flow in human colon cancer. All together, our results open the possibility that HBP links hyperglycemia, aberrant glycosylation and tumor malignancy, and suggest this pathway as a potential therapeutic target for colorectal cancer. |
