MACC1 promotes pancreatic cancer metastasis by interacting with the EMT regulator SNAI1.
MACC1 promotes pancreatic cancer metastasis by interacting with the EMT regulator SNAI1.
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DOI：
10.1038/s41419-022-05285-8
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发表时间：
2022-11-04
影响因子：
9
通讯作者：
Qin, Shanyu
中科院分区：
文献类型：
--
作者：
Zhang, Xianglian;Luo, Ya;Cen, Yu;Qiu, Xin;Li, Jing;Jie, Mengmeng;Yang, Shiming;Qin, Shanyu
转移是癌症相关死亡的主要原因。转移相关结肠癌蛋白1（MACC 1）在肿瘤转移中起着重要作用。然而，MACC 1在调节胰腺癌（PC）转移表型中的促转移作用仍然难以捉摸。在这里，我们报告MACC 1在癌症基因组图谱（TCGA）和组织微阵列（TMA）中高度表达，并被鉴定为预后不良的良好指标。PC细胞中MACC 1的过表达或敲低相应地以MET原癌基因受体酪氨酸激酶（MET）非依赖性方式促进或抑制胰腺癌细胞的迁移和侵袭。值得注意的是，PC细胞中MACC 1的敲低显著减少了肝转移模型中的肝转移病灶。从机制上讲，MACC 1与上皮-间质转化（EMT）调节因子蜗牛家族转录抑制因子1（SNAI 1）结合，通过上调SNAI 1的转录活性来驱动EMT，导致纤连蛋白1（FN 1）的反式激活和钙粘蛋白1（CDH 1）的反式抑制。总的来说，我们的研究结果揭示了MACC 1驱动胰腺癌细胞转移的新机制，并表明MACC 1-SNAI 1复合物介导的间质转化可能是胰腺癌的治疗靶点。
Metastasis is the dominant cause of cancer-related mortality. Metastasis-associated with colon cancer protein 1 (MACC1) has been proven to play a critical role in cancer metastasis. However, the prometastatic role of MACC1 in regulating the pancreatic cancer (PC) metastatic phenotype remains elusive. Here, we report that MACC1 is highly expressed in The Cancer Genome Atlas (TCGA) and tissue microarray (TMA) and identified as a good indicator for poor prognosis. Overexpression or knockdown of MACC1 in PC cells correspondingly promoted or inhibited pancreatic cancer cell migration and invasion in a MET proto-oncogene receptor tyrosine kinase (MET)-independent manner. Notably, knockdown of MACC1 in PC cells markedly decreased the liver metastatic lesions in a liver metastasis model. Mechanistically, MACC1 binds to the epithelial-mesenchymal transition (EMT) regulator snail family transcriptional repressor 1 (SNAI1) to drive EMT via upregulating the transcriptional activity of SNAI1, leading to the transactivation of fibronectin 1 (FN1) and the trans-repression of cadherin 1 (CDH1). Collectively, our results unveil a new mechanism by which MACC1 drives pancreatic cancer cell metastasis and suggest that the MACC1-SNAI1 complex-mediated mesenchymal transition may be a therapeutic target in pancreatic cancer.
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影响因子：
13.5
作者：
Lederer, Andri;Herrmann, Pia;Stein, Ulrike
通讯作者：
Stein, Ulrike
影响因子：
11.5
作者：
Lemos, Clara;Hardt, Markus S.;Stein, Ulrike
通讯作者：
Stein, Ulrike
DOI：
10.1083/jcb.201704053
发表时间：
2017-11-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Erdogan B;Ao M;White LM;Means AL;Brewer BM;Yang L;Washington MK;Shi C;Franco OE;Weaver AM;Hayward SW;Li D;Webb DJ
通讯作者：
Webb DJ
影响因子：
64.8
作者：
Konermann S;Brigham MD;Trevino AE;Joung J;Abudayyeh OO;Barcena C;Hsu PD;Habib N;Gootenberg JS;Nishimasu H;Nureki O;Zhang F
通讯作者：
Zhang F
影响因子：
2.9
作者：
Deer EL;González-Hernández J;Coursen JD;Shea JE;Ngatia J;Scaife CL;Firpo MA;Mulvihill SJ
通讯作者：
Mulvihill SJ