Ras/TGF-beta pathway downstream in liver metastasis of colorectal cancer

Ras/TGF-β通路下游在结直肠癌肝转移中的作用

基本信息

批准号：
21591731
负责人：
WATANABE Masahiko
金额：
$ 3万
依托单位：
Kitasato University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591731/
关键词：
大腸癌肝転移 TGF-beta PRL-3 K-ras 若年結腸癌 stage III MAPK PI3K

项目摘要

(Background) In colorectal cancer(CRC), K-ras mutation is found in nearly 40% of the patients, and it is of prognostic significance(Onozato W et al, J Surg Oncol, 2010). Moreover, its knockdown in CRC cell lines with mutated K-ras gene results in robust reduction of ability of cell proliferation and anchorage independent growth(Shirasawa S, Science, 1993), both of which reflect metastatic ability. On the other hand, robust alterations of glycan structures have been reported in CRC promotion steps, accompanied by remarkable phenotypic changes, however there is no report that mentions the relationship of K-ras mutation and glycan change.(Materials and Methods) We examined glycan change of CRC cell lines(DLD1 and HCT116) somatically knocked out for K-ras gene by lectin array including 41 lectins to elucidate whether K-ras mutation-induced glycan changes play a critical role in CRC promotion.(Result)(1) In DLD1, we compared DLD1wild type genotype cells(DLD1, DKS-5) with those that were knocked out for mutated K-ras gene(DKO-3, DKS-8), and the signals of MAL, MPA, UEA-I, and TJA-II were remarkably decreased in the knockdown cells.(2) In HCT116, we compared HCT116 wild type genotypic cells(HCT116, Hk2-10) with those that were knocked out for the mutated K-ras gene(Hke-3), and both MAL and MPA were remarkably declined.(3) In both cell lines, expression changes of glycans which can bind with MAL and MPA were consistent with the results of the lectin blotting, and both lectin signals were confirmed to be commonly altered by removing the mutated K-ras gene.(Conclusion) Mutated K-ras may be involved in critical phenotype change of CRC, accompanied by abnormal sialic acid recognition.

（背景）结直肠癌（CRC），在近40％的患者中发现K-RAS突变，并且具有预后意义（Onozato W等，J Surg Oncol，2010年）。此外，其在具有突变K-RAS基因的CRC细胞系中的敲低导致细胞增殖和锚定独立生长的能力降低（Shirasawa S，Science，1993），这两者都反映了转移性能力。 On the other hand, robust alterations of glycan structures have been reported in CRC promotion steps, accompanied by remarkable phenotypic changes, however there is no report that mentions the relationship of K-ras mutation and glycan change.(Materials and Methods) We examined glycan change of CRC cell lines(DLD1 and HCT116) somatically knocked out for K-ras gene by lectin array including 41 lectins to elucidate whether K-RAS突变引起的聚糖变化在CRC促进中起着至关重要的作用。（结果）（1）在DLD1中，我们将DLD1WILD型基因型基因型细胞（DLD1，DKS-5）与突变的K-RAS基因（DKO-3，DKS-8）和Mal，MAL，MPA，MPA，UEA，UEA-i-i-i-iea，uea-i-i的信号进行了比较。细胞。（2）在HCT116中，我们比较了HCT116野生型基因型细胞（HCT116，HK2-10）与被敲除突变的K-RAS基因（HKE-3）（HKE-3）（HKE-3）的野生型基因型细胞（HK2-10），MAL和MPA都显着下降。（3）在两种细胞系中都可以与MAL和MPA的表达变化，而MAL和MPA的表达变化是一致的。被证实通常通过去除突变的K-RAS基因来改变。（结论）突变的K-RAS可能与CRC的临界表型变化有关，并伴随着异常的唾液酸识别。