Overexpression of phosphoserine aminotransferase PSAT1 stimulates cell growth and increases chemoresistance of colon cancer cells.
BACKGROUND
Colorectal cancer (CRC) is one of the most common causes of cancer death throughout the world. In this work our aim was to study the role of the phosphoserine aminotransferase PSAT1 in colorectal cancer development.


RESULTS
We first observed that PSAT1 is overexpressed in colon tumors. In addition, we showed that after drug treatment, PSAT1 expression level in hepatic metastases increased in non responder and decreased in responder patients. In experiments using human cell lines, we showed that ectopic PSAT1 overexpression in colon carcinoma SW480 cell line resulted in an increase in its growth rate and survival. In addition, SW480-PSAT1 cells presented a higher tumorigenic potential than SW480 control cells in xenografted mice. Moreover, the SW480-PSAT1 cell line was more resistant to oxaliplatin treatment than the non-transfected SW480 cell line. This resistance resulted from a decrease in the apoptotic response and in the mitotic catastrophes induced by the drug treatment.


CONCLUSIONS
These results show that an enzyme playing a role in the L-serine biosynthesis could be implicated in colon cancer progression and chemoresistance and indicate that PSAT1 represents a new interesting target for CRC therapy.
Vié
Nadia
N
CNRS, UMR 5160, CRLC, 15, av, Charles Flahault, BP14491, 34093, Montpellier Cedex 5, France. nadia.vie@aldorel.fnclcc.fr
Copois
Virginie
V
Bascoul-Mollevi
Caroline
C
Denis
Vincent
V
Bec
Nicole
N
Robert
Bruno
B
Fraslon
Caroline
C
Conseiller
Emmanuel
E
Molina
Franck
F
Larroque
Christian
C
Martineau
Pierre
P
Del Rio
Maguy
M
Gongora
Céline
C
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000556:secondary; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D000637:Transaminases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000637:Transaminases; C022393:phosphoserine aminotransferase; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin