ACLY facilitates colon cancer cell metastasis by CTNNB1
ACLY facilitates colon cancer cell metastasis by CTNNB1
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ACLY通过CTNNB1促进结肠癌细胞转移
DOI：
10.1186/s13046-019-1391-9
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发表时间：
2019-09-12
影响因子：
11.3
通讯作者：
Zhao, Xiaoping
中科院分区：
文献类型：
--
作者：
Wen, Jun;Min, Xuejie;Zhao, Xiaoping
背景结肠癌是全球第二大癌症。复发和化疗耐药在晚期结肠癌中非常常见。ATP-柠檬酸裂解酶(ACLY)是脂质合成的第一步速率控制酶，在结肠癌中升高。然而，ACLY在结肠癌转移中的确切作用尚不清楚。方法为了评价ACLY在结肠癌转移中的作用，我们在两个ACLY缺陷的结肠癌细胞系中进行了细胞迁移和侵袭实验。采用小鼠结肠癌模型，观察ACLY对小鼠结肠转移潜能的影响。对78例结肠癌患者ACLY与CTNNB1蛋白的相关性进行了皮尔逊相关分析。为了探讨ACLY与CTNNB1的关系，我们通过免疫印迹、迁移和侵袭实验证实了ACLY可能通过CTNNB1调控细胞的转移。此外，我们还介绍了ACLY在体内外促进结肠癌转移的机制。ACLY可通过相互作用稳定CTNNB1(β-catenin 1)蛋白，该复合体可能促进CTNNB1通过胞浆转位到胞核，进而促进CTNNB1的转录活性和迁移侵袭能力。78例结肠癌患者的免疫组织化学分析显示，ACLY和CTNNB1蛋白的高表达与结肠癌的转移呈正相关。结论进一步揭示了结肠癌转移的分子机制，有助于提高治疗效果。
BackgroundColon cancer is the second leading cancer worldwide. Recurrent disease and chemotherapeutic drug resistance are very common in the advanced stage of colon cancer. ATP-citrate lyase (ACLY), the first-step rate-controlling enzyme in lipid synthesis, is elevated in colon cancer. However, it remains unclear about the exact role of ACLY in the development of colon cancer metastasis.MethodsTo evaluate the role of ACLY in colon cancer metastasis, we performed cell migration and invasion assays in two ACLY-deficient colon cancer cell lines. Colon cancer mouse model is used to examine ACLY’s effects on colon metastasis potentials in vivo. We analyzed the correlation between ACLY and CTNNB1 protein in 78 colon cancer patients by Pearson correlation. To finally explore the relationship of ACLY and CTNNB1, we used western blots, migration and invasion assays to confirm that ACLY may regulate metastasis by CTNNB1.ResultsOur data showed that the abilities of cell migration and invasion were attenuated in ACLY-deficient HCT116 and RKO cell lines. Furthermore, we describe the mechanism of ACLY in promoting colon cancer metastasis in vitro and in vivo. ACLY could stabilize CTNNB1 (beta-catenin 1) protein by interacting, and the complex might promote CTNNB1 translocation through cytoplasm to nucleus, subsequently promote the CTNNB1 transcriptional activity and migration and invasion abilities of colon cancer cells. Immunohistochemical analysis of 78 colon cancer patients showed that the high expression levels of ACLY and CTNNB1 protein was positively correlated with metastasis of colon cancer.ConclusionsThese results shed new light on the molecular mechanism underlying colon cancer metastasis, which might help in improving therapeutic efficacy.