Capillary morphogenesis gene 2 maintains gastric cancer stem-like cell phenotype by activating a Wnt/β-catenin pathway.
Capillary morphogenesis gene 2 maintains gastric cancer stem-like cell phenotype by activating a Wnt/β-catenin pathway.
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DOI：
10.1038/s41388-018-0226-z
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发表时间：
2018-07
期刊：
影响因子：
8
通讯作者：
Bian X
中科院分区：
文献类型：
--
作者：
Ji C;Yang L;Yi W;Xiang D;Wang Y;Zhou Z;Qian F;Ren Y;Cui W;Zhang X;Zhang P;Wang JM;Cui Y;Bian X
越来越多的证据表明，胃癌的发生发展主要与胃癌干细胞样细胞(GCSLCs)的存在有关。然而，目前还不清楚GCSLC的数量是如何维持的。本研究旨在探讨毛细血管形态发生基因2(CMG2)在GCSLC维持中的作用及其与GC进展的关系。研究发现，CMG2在胃癌组织中高表达，其表达水平与胃癌的侵袭深度和淋巴结转移有关，与胃癌患者的生存期呈负相关。分选的CMG2高GC细胞优先聚集在CD44High干细胞样细胞群中，CD44High干细胞样细胞群体表达高水平的干性相关基因，具有更强的自我更新和致瘤能力。CMG2基因缺失导致GC细胞中GCSLC数量减少，干性减弱，侵袭和转移能力降低，上皮-间充质转化表型减弱。在机制上，CmG2与LRP6在GCSLC中相互作用，激活Wnt/β-连环蛋白途径。因此，我们的结果表明，CMG2通过维持GCSLC促进GC进展，并可作为新的预后指标和人类GC治疗的靶点。
A growing body of evidence shows that the development and progression of gastric cancer (GC) is mainly associated to the presence of gastric cancer stem-like cells (GCSLCs). However, it is unclear how GCSLC population is maintained. This study aimed to explore the role of capillary morphogenesis gene 2 (CMG2) in GCSLC maintenance and the relevance to GC progression. We found that CMG2 was highly expressed in GC tissues and the expression levels were associated with the invasion depth and lymph node metastasis of GC, and inversely correlated with the survival of GC patients. Sorted CMG2High GC cells preferentially clustered in CD44High stem-like cell population, which expressed high levels of stemness-related genes with increased capabilities of self-renewal and tumorigenicity. Depletion of CMG2 gene resulted in reduction of GCSLC population with attenuated stemness and decrease of invasive and metastatic capabilities with subdued epithelial–mesenchymal transition phenotype in GC cells. Mechanistically, CMG2 interacted with LRP6 in GCSLCs to activate a Wnt/β-catenin pathway. Thus, our results demonstrate that CMG2 promotes GC progression by maintaining GCSLCs and can serve as a new prognostic indicator and a target for human GC therapy.
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