Expression and the role of 3'-phosphoadenosine 5'-phosphosulfate transporters in human colorectal carcinoma.
Sulfation represents an essential modification for various molecules and regulates many biological processes. The sulfation of glycans requires a specific transporter for 3'-phosphoadenosine 5'-phosphosulfate (PAPS) on the Golgi apparatus. This study investigated the expression of PAPS transporter genes in colorectal carcinomas and the significance of Golgi-specific sulfation in the proliferation of colorectal carcinoma cells. The relative amount of PAPST1 transcripts was found to be higher than those of PAPST2 in colorectal cancerous tissues. Immunohistochemically, the enhanced expression of PAPST1 was observed in fibroblasts in the vicinity of invasive cancer cells, whereas the expression of PAPST2 was decreased in the epithelial cells. RNA interference of either of the two PAPS transporter genes reduced the extent of sulfation of cellular proteins and cellular proliferation of DLD-1 human colorectal carcinoma cells. Silencing the PAPS transporter genes reduced fibroblast growth factor signaling in DLD-1 cells. These findings indicate that PAPS transporters play a role in the proliferation of colorectal carcinoma cells themselves and take part in a desmoplastic reaction to support cancer growth by controlling their sulfation status.
Department of Bioinformatics, Soka University, Tokyo, Japan.
Shin
S
Kamiyama
Tomomi
T
Ichimiya
Yuzuru
Y
Ikehara
Tomofumi
T
Takase
Izumi
I
Fujimoto
Takeshi
T
Suda
Shoji
S
Nakamori
Mitsuru
M
Nakamura
Fumiaki
F
Nakayama
Tatsuro
T
Irimura
Hayao
H
Nakanishi
Masahiko
M
Watanabe
Hisashi
H
Narimatsu
Shoko
S
Nishihara
D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004338:Drug Combinations; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010724:Phosphoadenosine Phosphosulfate / Q000378:metabolism; D011134:Polysaccharides / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000235:genetics; D013422:Sulfamonomethoxine / Q000378:metabolism; D000076988:Sulfate Transporters; D014295:Trimethoprim / Q000378:metabolism; D014407:Tumor Cells, Cultured
D027321:Anion Transport Proteins; D004338:Drug Combinations; D026901:Membrane Transport Proteins; D011134:Polysaccharides; D012333:RNA, Messenger; C476248:SLC35B2 protein, human; C510864:SLC35B3 protein, human; D000076988:Sulfate Transporters; C062251:sulfaton; D010724:Phosphoadenosine Phosphosulfate; D014295:Trimethoprim; D013422:Sulfamonomethoxine