韓國(guó)科學(xué)家1月31日說(shuō),,他們發(fā)現(xiàn)一種能抑制人類大腸癌細(xì)胞的受體基因,,對(duì)治療腸癌具有參考價(jià)值。
最近一期的美國(guó)《分子細(xì)胞》雜志刊登了這一發(fā)現(xiàn),。研究認(rèn)為,,這種基因未來(lái)可用于快速檢測(cè)與治療大腸癌。
由韓國(guó)首爾大學(xué)生物科學(xué)教授白圣熙(音譯)與淑明女子大學(xué)生物學(xué)教授金芹日(音譯)牽頭的研究團(tuán)隊(duì)發(fā)現(xiàn),,磷酸化維甲酸α孤受體(ROR-α)可以影響腫瘤細(xì)胞生長(zhǎng),。
α孤受體發(fā)現(xiàn)于30年前,當(dāng)時(shí)因會(huì)給小腦帶來(lái)問(wèn)題,、導(dǎo)致肌肉萎縮及骨質(zhì)疏松而為人所知,。
“α孤受體磷酸化后可以破壞β-catenin蛋白,進(jìn)而抑制大腸癌的擴(kuò)散,,”白圣熙說(shuō),。
正因?yàn)榱姿峄?alpha;孤受體可抑制大腸癌,因此,,在自然狀態(tài)下,,金芹日說(shuō),大腸癌患者體內(nèi)α孤受體磷酸化程度較低,。對(duì)30名大腸癌患者展開的檢測(cè)結(jié)果顯示,,癌細(xì)胞擴(kuò)散時(shí)α孤受體磷酸化降低70%。
“這一幅度相當(dāng)大,,”白圣熙說(shuō),。
不過(guò),科學(xué)家發(fā)現(xiàn),,可借助絲氨酸中的蛋白激酶C(PKC)來(lái)重新激活α孤受體的磷酸化,。
白圣熙說(shuō),除腸癌外,,這種受體基因還有助其他癌癥與骨質(zhì)疏松的研究,。
過(guò)去4年中,韓國(guó)國(guó)家科學(xué)基金會(huì)向這一研究團(tuán)隊(duì)提供約5億韓元(約43.1萬(wàn)美元)研究經(jīng)費(fèi),。研究團(tuán)隊(duì)計(jì)劃未來(lái)集中研究這種受體基因,,以期尋找臨床治療腸癌途徑,。(生物谷Bioon.com)
生物谷推薦原始出處:
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.