肝激酶B1与肺癌发生发展关系的研究现状

Role and underlying mechanism of liver kinase B1 in lung cancerigenesis and progression

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.