Vié Nadia, Copois Virginie, Bascoul-Mollevi Caroline, Denis Vincent, Bec Nicole, Robert Bruno, Fraslon Caroline, Conseiller Emmanuel, Molina Franck, Larroque Christian, Martineau Pierre, Del Rio Maguy, Gongora Céline
CNRS, UMR 5160, CRLC, 15, av, Charles Flahault, BP14491, 34093, Montpellier Cedex 5, France.
Mol Cancer. 2008 Jan 25;7:14. doi: 10.1186/1476-4598-7-14.
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.
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.
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.
结直肠癌(CRC)是全球癌症死亡的最常见原因之一。在本研究中,我们的目的是探讨磷酸丝氨酸转氨酶PSAT1在结直肠癌发生发展中的作用。
我们首先观察到PSAT1在结肠肿瘤中过表达。此外,我们发现药物治疗后,肝转移患者中,无反应者的肝转移灶中PSAT1表达水平升高,而有反应者降低。在使用人细胞系的实验中,我们发现结肠癌细胞系SW480中异位过表达PSAT1会导致其生长速率和存活率增加。此外,在异种移植小鼠中,SW480-PSAT1细胞比SW480对照细胞具有更高的致瘤潜能。而且,SW480-PSAT1细胞系比未转染的SW480细胞系对奥沙利铂治疗更具抗性。这种抗性源于药物治疗诱导的凋亡反应和有丝分裂灾难的减少。
这些结果表明,一种参与L-丝氨酸生物合成的酶可能与结肠癌进展和化疗耐药有关,提示PSAT1是结直肠癌治疗中一个新的有趣靶点。