FUCA1 is induced by wild-type p53 and expressed at different levels in thyroid cancers depending on p53 status.
FUCA1 is induced by wild-type p53 and expressed at different levels in thyroid cancers depending on p53 status.
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DOI：
10.3892/ijo.2017.3968
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发表时间：
2017-06
影响因子：
5.2
通讯作者：
N. Tsuchida;M. Ikeda;Υoshizumu Ιshino;M. Grieco;G. Vecchio
中科院分区：
文献类型：
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作者：
N. Tsuchida;M. Ikeda;Υoshizumu Ιshino;M. Grieco;G. Vecchio
细胞表面聚糖的聚焦残基通过聚焦转移酶（FUTs）添加，α-L-聚焦酶（FUCAs）去除，在细胞生长、侵袭和转移过程中发挥重要作用。通过差异显示法，我们分离出α-L-聚焦酶-1（编码溶酶体聚焦酶-1酶的基因）的一个3'非编码区作为野生型p53诱导基因：在允许温度下，转染温度敏感型p53突变体的Saos-2细胞中诱导了18S和20S FUCA1 mRNA物种。通过对甲状腺癌活检样本的微阵列分析，FUCA1 RNA在间变性甲状腺癌样本（ATCs）中的表达水平较低，而在乳头状甲状腺癌样本（ptc）和正常甲状腺组织中的表达水平较高。由于大多数ATCs被报道携带p53的突变形式，而ptc主要携带p53的野生型形式，因此在甲状腺癌中，FUCA1的表达水平可能至少在一定程度上受到p53状态的调节。为了更好地了解FUCA基因在甲状腺肿瘤发生中的作用，我们检测了转染FUCA1或FUCA2（后者编码一种分泌的非溶酶体酶）的甲状腺细胞系的体外克隆潜能。我们发现α-L-聚焦酶并没有抑制细胞的生长。与我们观察到的FUCA1表达相反，FUT8在ATCs中表达水平高，而在ptc和正常甲状腺组织中表达水平低。综上所述，这些结果表明，与侵袭性较低的ptc相比，侵袭性ATCs在细胞表面聚糖上的较高聚焦水平可能至少在一定程度上导致了ATCs比ptc更具侵袭性和转移性的表型，因为FUCA1和FUT8的表达水平在这两种类型的癌症中呈负相关。
Fucose residues of cell surface glycans, which play important roles in growth, invasion and metastasis, are added by fucosyltransferases (FUTs) and removed by α-L-fucosidases (FUCAs). By the differential display method, we isolated a 3' non-coding region of α-L-fucosidase-1 (FUCA1) (a gene coding for the lysosomal fucosidase-1 enzyme) as a wild-type p53-inducible gene: 18S and 20S FUCA1 mRNA species were induced in Saos-2 cells transfected with a temperature-sensitive p53 mutant at the permissive temperature. By microarray analyses of thyroid cancer biopsy samples, FUCA1 RNA expression levels were found to be lower in anaplastic thyroid cancer samples (ATCs), while they were higher in papillary thyroid cancer samples (PTCs) and in normal thyroid tissues. Since most ATCs were reported to carry the mutated form of p53, while PTCs carry mostly the wild-type form of p53, it is likely that FUCA1 expression levels are regulated, at least in part, by the p53 status in thyroid cancers. In order to better understand the role played by FUCA genes in thyroid tumorigenesis, we examined the clonogenic potential in vitro of thyroid cell lines transfected with either FUCA1 or FUCA2 (the latter gene coding for a secreted, non-lysosomal enzyme). We found that α-L-fucosidases did not suppress grossly cell growth. Contrary to what we observed with the expression of FUCA1, the FUT8 expression levels were found high in ATCs but lower in PTCs and normal thyroid tissues. Taken together, these results suggest the possibility that the higher fucose levels on cell surface glycans of aggressive ATCs, compared to those of less aggressive PTCs, may be at least in part responsible for the more aggressive and metastatic phenotype of ATCs compared to PTCs, as the expression levels of FUCA1 and FUT8 were inversely related in these two types of cancers.