MICAL1 facilitates pancreatic cancer proliferation, migration, and invasion by activating WNT/β-catenin pathway.
MICAL1 facilitates pancreatic cancer proliferation, migration, and invasion by activating WNT/β-catenin pathway.
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MICAL1 通过激活 WNT/β-catenin 通路促进胰腺癌增殖、迁移和侵袭
DOI：
10.1186/s12967-022-03749-1
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发表时间：
2022-11-12
影响因子：
7.4
通讯作者：
Yu, Chao
中科院分区：
文献类型：
--
作者：
Cai, Kun;Deng, Lu;Zheng, Dijie;Li, Lin;He, Zhiwei;Yu, Chao
mical1参与多种癌症的恶性过程；然而，MICAL1在胰腺癌（PC）中的作用尚未得到很好的表征。本研究旨在探讨MICAL1在PC中的表达及功能。方法采用srt - qpcr和免疫组化检测MICAL1在PC及癌旁非肿瘤组织中的表达。通过细胞计数试剂盒-8、EdU、克隆形成、创面愈合、Transwell实验以及动物模型研究MICAL1过表达或抑制表达对PC细胞增殖、侵袭和转移的影响。RNA-seq用于探索MICAL1功能的主要途径。采用蛋白质组学、质谱法和共免疫沉淀法研究蛋白与MICAL1的相互作用。进行了救援实验来验证这些发现。结果与匹配的癌旁非肿瘤组织相比，PC组织MICAL1 mRNA和蛋白水平均上调。MICAL1的表达水平与PC的增殖和转移状态有关。MICAL1的抑制在体外和体内显著抑制了PC细胞的生长、迁移和侵袭。RNA测序分析表明MICAL1与WNT通路密切相关。MICAL1过表达(1)促进了TBC1D1 Ser660位点的磷酸化，(2)促进了FZD7在细胞膜上的分布，(3)抑制了FZD7在溶酶体中的降解，(4)激活了WNT通路。结论smical1在PC中表达上调，并通过激活WNT/β-catenin信号通路参与刺激PC细胞的进程。因此，MICAL1是一个潜在的治疗PC的靶点。
BackgroundMICAL1 is involved in the malignant processes of several types of cancer; however, the role of MICAL1 in pancreatic cancer (PC) has not been well-characterized. This study aimed to investigate the expression and function of MICAL1 in PC.MethodsRT-qPCR and immunohistochemistry were used to detect MICAL1 expression in PC and adjacent nontumor tissues. Cell Counting Kit-8, EdU, clone formation, wound healing, and Transwell assays as well as animal models were used to investigate the effects of overexpression or inhibition of MICAL1 expression on the proliferation, invasion, and metastasis of PC cells. RNA-seq was used to explore the main pathway underlying the functions of MICAL1. Proteomics, mass spectrometry, and co-immunoprecipitation assays were used to investigate the interaction of proteins with MICAL1. Rescue experiments were conducted to validate these findings.ResultsBoth MICAL1 mRNA and protein levels were upregulated in PC tissues compared with matched adjacent nontumor tissues. The expression level of MICAL1 was associated with the proliferative and metastatic status of PC. Repression of MICAL1 significantly inhibited PC cell growth, migration, and invasion in vitro and in vivo. RNA sequencing analysis indicated that MICAL1 was closely correlated with the WNT pathway. Overexpression of MICAL1 (1) promoted the phosphorylation of TBC1D1 at the Ser660 site, (2) facilitated the distribution of FZD7 on the cytomembrane, (3) inhibited the degradation of FZD7 in the lysosome, and (4) activated the WNT pathway.ConclusionsMICAL1 was upregulated in PC and involved in stimulating the progression of PC cells by activating the WNT/β-catenin signaling pathway. Therefore, MICAL1 is a potential therapeutic target for PC.
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影响因子：
16.6
作者：
Kozielewicz, Pawel;Turku, Ainoleena;Schulte, Gunnar
通讯作者：
Schulte, Gunnar
MSRB1和Micals通过可逆的立体选择性蛋氨酸氧化来调节肌动蛋白的组装和巨噬细胞功能。
影响因子：
16
作者：
Lee, Byung Cheon;Peterfi, Zalan;Hoffmann, Fukun W.;Moore, Richard E.;Kaya, Alaattin;Avanesov, Andrei;Tarrago, Lionel;Zhou, Yani;Weerapana, Eranthie;Fomenko, Dmitri E.;Hoffmann, Peter R.;Gladyshev, Vadim N.
通讯作者：
Gladyshev, Vadim N.
影响因子：
3.7
作者：
Qin XB;Zhang WJ;Zou L;Huang PJ;Sun BJ
通讯作者：
Sun BJ
DOI：
10.1016/j.cub.2018.01.025
发表时间：
2018-05-07
期刊：
Current biology : CB
影响因子：
--
作者：
Alto LT;Terman JR
通讯作者：
Terman JR
MICAL1 通过调节乳腺癌细胞的氧化应激来控制细胞侵袭表型
影响因子：
3.8
作者：
Deng W;Wang Y;Gu L;Duan B;Cui J;Zhang Y;Chen Y;Sun S;Dong J;Du J
通讯作者：
Du J