S100A8 promotes epithelial-mesenchymal transition and metastasis under TGF-β/USF2 axis in colorectal cancer.
S100A8 promotes epithelial-mesenchymal transition and metastasis under TGF-β/USF2 axis in colorectal cancer.
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S100A8 促进结直肠癌中 TGF-β/USF2 轴下的上皮间质转化和转移。
DOI：
10.1002/cac2.12130
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Xu F
中科院分区：
文献类型：
--
作者：
Li S;Zhang J;Qian S;Wu X;Sun L;Ling T;Jin Y;Li W;Sun L;Lai M;Xu F
转化生长因子β (TGF - β)通路在诱导上皮-间充质转化（epithelial - mesenchymal transition， EMT）中起关键作用，而EMT是肿瘤侵袭转移的关键步骤。然而，TGF‐β在结直肠癌（CRC）中诱导EMT的调控机制尚未完全阐明。在以往的研究中，发现S100A8可能调控EMT。本研究旨在阐明S100A8在TGF - β -诱导的EMT中的作用，并探讨其在CRC中的潜在机制。免疫组化检测412例结直肠癌组织中S100A8和上游转录因子2 （USF2）的表达。Kaplan - Meier生存分析。在体外，采用Western blot、迁移和侵袭实验研究S100A8和USF2对TGF - β -诱导的EMT的影响。采用小鼠转移模型测定体内转移能力。采用荧光素酶报告基因法和染色质免疫沉淀法探讨USF2在S100A8转录中的作用。在TGF‐β‐诱导的CRC细胞EMT过程中，S100A8和转录因子USF2上调。S100A8促进细胞迁移、侵袭和EMT。USF2通过直接结合S100A8的启动子区转录调控S100A8的表达。此外，TGF‐β增强了CRC细胞的USF2/S100A8信号轴，而胞外S100A8则抑制了CRC细胞的USF2/S100A8信号轴。S100A8在结直肠癌肿瘤细胞中的表达与较差的总生存率相关。肿瘤细胞中USF2表达与S100A8表达呈正相关，而与S100A8阳性基质细胞表达负相关。TGF‐β通过USF2/S100A8轴促进结直肠癌的EMT和转移，而胞外S100A8抑制USF2/S100A8轴。USF2被认为是细胞内和细胞外S100A8反馈回路的一个重要开关。在结直肠癌中，肿瘤细胞中的S100A8预示预后不良，而基质细胞中的S100A8预示预后良好。我们首先证明了TGF‐β通过上调细胞内USF2/S100A8轴促进转移，而USF2可能是细胞内和细胞外S100A8相反功能的开关。
The transforming growth factor‐β (TGF‐β) pathway plays a pivotal role in inducing epithelial‐mesenchymal transition (EMT), which is a key step in cancer invasion and metastasis. However, the regulatory mechanism of TGF‐β in inducing EMT in colorectal cancer (CRC) has not been fully elucidated. In previous studies, it was found that S100A8 may regulate EMT. This study aimed to clarify the role of S100A8 in TGF‐β‐induced EMT and explore the underlying mechanism in CRC. S100A8 and upstream transcription factor 2 (USF2) expression was detected by immunohistochemistry in 412 CRC tissues. Kaplan‐Meier survival analysis was performed. In vitro, Western blot, and migration and invasion assays were performed to investigate the effects of S100A8 and USF2 on TGF‐β‐induced EMT. Mouse metastasis models were used to determine in vivo metastasis ability. Luciferase reporter and chromatin immunoprecipitation assay were used to explore the role of USF2 on S100A8 transcription. During TGF‐β‐induced EMT in CRC cells, S100A8 and the transcription factor USF2 were upregulated. S100A8 promoted cell migration and invasion and EMT. USF2 transcriptionally regulated S100A8 expression by directly binding to its promoter region. Furthermore, TGF‐β enhanced the USF2/S100A8 signaling axis of CRC cells whereas extracellular S100A8 inhibited the USF2/S100A8 axis of CRC cells. S100A8 expression in tumor cells was associated with poor overall survival in CRC. USF2 expression was positively related to S100A8 expression in tumor cells but negatively related to S100A8‐positive stromal cells. TGF‐β was found to promote EMT and metastasis through the USF2/S100A8 axis in CRC while extracellular S100A8 suppressed the USF2/S100A8 axis. USF2 was identified as an important switch on the intracellular and extracellular S100A8 feedback loop. In colorectal cancer, S100A8 in tumor cells predicts poor prognosis but that in stroma cells indicates good prognosis. We first proved that TGF‐β promotes metastasis through upregulated intracellular USF2/S100A8 axis, and USF2 maybe is the switcher on the opposite function of intracellular and extracellular S100A8.
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影响因子：
16.2
作者：
Feng, Rui-Mei;Zong, Yi-Nan;Xu, Rui-Hua
通讯作者：
Xu, Rui-Hua
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影响因子：
4.6
作者：
Li H;Zhong A;Li S;Meng X;Wang X;Xu F;Lai M
通讯作者：
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影响因子：
4.4
作者：
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通讯作者：
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影响因子：
9.7
作者：
Morrison, Chevaun D.;Parvani, Jenny G.;Schiemann, William P.
通讯作者：
Schiemann, William P.
影响因子：
10.5
作者：
GREGOR, PD;SAWADOGO, M;ROEDER, RG
通讯作者：
ROEDER, RG