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SCI 3 August 2019 An Lkb1-Sik axis suppresses lung tumor growth and controls differentiation
The kinase, LKB1, is a critical tumor suppressor in sporadic and familial human cancers, yet the mechanisms by which it suppresses tumor growth remain poorly understood. To investigate the tumor-suppressive capacity of four canonical families of Lkb1 substrates in vivo, we employed CRISPR/Cas9-mediated combinatorial genome editing in a mouse model of oncogenic K-ras driven lung adenocarcinoma. We demonstrate that members of the salt-inducible kinase (Sik) family are critical for constraining tumor development. 在散发性和家族性人类癌症中LKB1激酶是一种关键的肿瘤抑制因子，但其抑制肿瘤生长的机制仍知之甚少。为了研究Lkb1底物的4个典型家族在体内的抑癌能力，我们采用CRISPR/ cas9介导的组合基因组编辑技术对K-ras癌基因驱动的肺腺癌小鼠模型进行了研究。我们证明，盐诱导激酶(Sik)家族成员对抑制肿瘤的进展至关重要。 Histological and gene expression similarities between Lkb1- and Sik-deficient tumors suggest that Siks and Lkb1 operate within the same axis. Furthermore, a gene expression signature reflecting Sik deficiency is enriched in LKB1 mutant human lung adenocarcinomas and is regulated by LKB1 in human cancer cell lines. Together, these findings reveal a key Lkb1-Sik tumor-suppressive axis and underscore the need to redirect efforts to elucidate the mechanisms through which LKB1 mediates tumor suppression. Lkb1和Sik缺陷的肿瘤组织学和基因表达的相似性表明Siks和Lkb1在同一轴上发挥。作用，此外，反映Sik缺陷的基因表达特征在LKB1突变体人肺腺癌中丰富存在，且在人癌细胞系中受LKB1调控。总之，这些发现揭示了一个关键的LKB1- Sik肿瘤抑制轴，并强调有必要重新努力阐明LKB1介导肿瘤抑制的机制。 喜欢SCI天天读的理由 陪您一起学习SCI医学论文 每天5分钟，让自己的英语牛逼起来 特殊福利让您惊喜连连 |
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