韩国科学家1月31日说,他们发现一种能抑制人类大肠癌细胞的受体基因,对治疗肠癌具有参考价值。
最近一期的美国《分子细胞》杂志刊登了这一发现。研究认为,这种基因未来可用于快速检测与治疗大肠癌。
由韩国首尔大学生物科学教授白圣熙(音译)与淑明女子大学生物学教授金芹日(音译)牵头的研究团队发现,磷酸化维甲酸α孤受体(ROR-α)可以影响肿瘤细胞生长。
α孤受体发现于30年前,当时因会给小脑带来问题、导致肌肉萎缩及骨质疏松而为人所知。
“α孤受体磷酸化后可以破坏β-catenin蛋白,进而抑制大肠癌的扩散,”白圣熙说。
正因为磷酸化α孤受体可抑制大肠癌,因此,在自然状态下,金芹日说,大肠癌患者体内α孤受体磷酸化程度较低。对30名大肠癌患者展开的检测结果显示,癌细胞扩散时α孤受体磷酸化降低70%。
“这一幅度相当大,”白圣熙说。
不过,科学家发现,可借助丝氨酸中的蛋白激酶C(PKC)来重新激活α孤受体的磷酸化。
白圣熙说,除肠癌外,这种受体基因还有助其他癌症与骨质疏松的研究。
过去4年中,韩国国家科学基金会向这一研究团队提供约5亿韩元(约43.1万美元)研究经费。研究团队计划未来集中研究这种受体基因,以期寻找临床治疗肠癌途径。(生物谷Bioon.com)
生物谷推荐原始出处:
Molecular Cell, Volume 37, Issue 2, 183-195, 29 January 2010 | 10.1016/j.molcel.2009.12.022
RORα Attenuates Wnt/β-Catenin Signaling by PKCα-Dependent Phosphorylation in Colon Cancer
Ji Min Lee, Ik Soo Kim, Hyunkyung Kim, Jason S. Lee, Kyeongkyu Kim, Hwa Young Yim, Jiyeong Jeong, Jung Hwa Kim, Ji-Young Kim, Hanna Lee, Sang-Beom Seo, Hogeun Kim, Michael G. Rosenfeld, Keun Il Kim, Sung Hee Baek
Wnt family members play diverse roles in development and disease. Noncanonical Wnt ligands can inhibit canonical Wnt signaling depending on the cellular context; however, the underlying mechanism of this antagonism remains poorly understood. Here we identify a specific mechanism of orphan nuclear receptor RORα-mediated inhibition of canonical Wnt signaling in colon cancer. Wnt5a/PKCα-dependent phosphorylation on serine residue 35 of RORα is crucial to link RORα to Wnt/β-catenin signaling, which exerts inhibitory function of the expression of Wnt/β-catenin target genes. Intriguingly, there is a significant correlation of reduction of RORα phosphorylation in colorectal tumor cases compared to their normal counterpart, providing the clinical relevance of the findings. Our data provide evidence for a role of RORα, functioning at the crossroads between the canonical and the noncanonical Wnt signaling pathways, in mediating transrepression of the Wnt/β-catenin target genes, thereby providing new approaches for the development of therapeutic agents for human cancers.