Hyperglycemia exacerbates colon cancer malignancy through hexosamine biosynthetic pathway.
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.
Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brazil.
A
A
Vasconcelos-Dos-Santos
Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brazil.
H F B R
HF
Loponte
Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brazil.
N R
NR
Mantuano
Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brazil.
I A
IA
Oliveira
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
I F
IF
de Paula
Programa de Biologia Celular, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil.
L K
LK
Teixeira
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
J C M
JC
de-Freitas-Junior
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
K C
KC
Gondim
Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brazil.
N
N
Heise
Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brazil.
R
R
Mohana-Borges
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
J A
JA
Morgado-Díaz
Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brazil.
W B
WB
Dias
Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brazil.
A R
AR
Todeschini