摘要
目的:对肝激酶B1(LKB1)的结构、功能及其与肺癌相关性的研究进展进行概述。方法:应用PubMed及CNKI期刊全文数据库检索系统,以"肝激酶B1和肺癌"为关键词,检索1998-2011年的相关文献。纳入标准:1)LKB1的结构和生物学功能;2)在肺癌细胞中LKB1基因的突变;3)LKB1与肺癌的发生和发展。根据纳入标准分析文献30篇。结果:LKB1,也称为丝氨酸/苏氨酸蛋白激酶11(STK11),在调节能量代谢、细胞生长和细胞极性等方面发挥重要作用。LKB1的胚系突变导致多发性息肉综合征(PJS)。在多数散发的肿瘤中,LKB1体细胞突变罕见,但在非小细胞肺癌(NSCLC)中,LKB1突变率可高达20%~30%。近年来的研究结果表明,LKB1的缺失促进K-ras突变活化诱发的肺部肿瘤的发展和转移。LKB1与肺癌细胞的分化、上皮细胞间质化、肺癌细胞的侵袭和脱落凋亡等肿瘤转移过程中的重要事件相关。结论:LKB1抑制肺癌的发生和转移,为肺癌的分子靶向治疗提供了潜在的靶点。
OBJECTIVE: To review the recent advances in studies of structure and function of liver kinase B1 (LKB1) and its relevance to lung cancer. METHODS: Articles were found in Pubmed and CNKI from the year 1998 to 2011 with "LKBl,lung cancer" as key words. Choice criteria: 1) molecular structure and biological functions of LKB1; 2) LKB1 gene mutations in lung cancer;3) LKB1 and lung cancerigenesis and progression. According to the above crite- ria, 30 papers were analyzed and reviewed. RESULTS: LKB1, as a serine/threonine kinase and tumor suppressor, plays significant roles in regulation of cellular metabolism, cell growth and cell polarity. Germline mutation of LKB1 results in Peutz-Jeghers syndrome. Although uncommon in most sporadic cancers,inactivating somatic mutation rate of LKB1 has been reported to be 20 %- 30 % in non-small cell lung cancer. Recent studies have provided strong evidences that Lkbl loss facilitates progression and metastasis in Kras-induced lung cancers. Further investigation indicated that LKB1 is involved with key events of tumor metastatic progress including regulation of lung cancer cell differentiation, epithelial mesenchy- mal transition,cell invasion and anoikis. CONCLUSION: LKB1 functions as a barrier in pulmonary tumorigenesis and metastasis, providing potential target for clinical molecular target therapy.
出处
《中华肿瘤防治杂志》
CAS
北大核心
2012年第21期1672-1675,共4页
Chinese Journal of Cancer Prevention and Treatment
基金
国家自然科学基金(30971307
81071915)
天津市应用基础及前沿技术研究(10JCYBJC13700)
天津市卫生局科技基金(2011KZ107)
关键词
LKB1
肺癌
转移
抑癌基因
LKB1
lung cancer
metastasis
tumor suppressor gene