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αvβ3整合素诱导部分上皮-间质转化，不依赖于转化生长因子-β信号通路。

αvβ3 Integrin induces partial EMT independent of TGF-β signaling.

作者信息

Kariya Yoshinobu, Oyama Midori, Suzuki Takato, Kariya Yukiko

机构信息

Department of Biochemistry, Fukushima Medical University School of Medicine, Fukushima City, 960-1295, Japan.

Laboratory Animal Research Center, Fukushima Medical University School of Medicine, Fukushima City, 960-1295, Japan.

出版信息

Commun Biol. 2021 Apr 21;4(1):490. doi: 10.1038/s42003-021-02003-6.

DOI:10.1038/s42003-021-02003-6
PMID:33883697
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8060333/
Abstract

Epithelial-mesenchymal transition (EMT) plays a pivotal role for tumor progression. Recent studies have revealed the existence of distinct intermediate states in EMT (partial EMT); however, the mechanisms underlying partial EMT are not fully understood. Here, we demonstrate that αvβ3 integrin induces partial EMT, which is characterized by acquiring mesenchymal phenotypes while retaining epithelial markers. We found αvβ3 integrin to be associated with poor survival in patients with lung adenocarcinoma. Moreover, αvβ3 integrin-induced partial EMT promoted migration, invasion, tumorigenesis, stemness, and metastasis of lung cancer cells in a TGF-β-independent fashion. Additionally, TGF-β1 promoted EMT progression synergistically with αvβ3 integrin, while a TGF-β signaling inhibitor showed no effect on αvβ3 integrin-induced partial EMT. Meanwhile, the microRNA-200 family abolished the αvβ3 integrin-induced partial EMT by suppressing αvβ3 integrin cell surface expression. These findings indicate that αvβ3 integrin is a key inducer of partial EMT, and highlight a new mechanism for cancer progression.

摘要

上皮-间质转化（EMT）在肿瘤进展中起关键作用。最近的研究揭示了EMT中存在不同的中间状态（部分EMT）；然而，部分EMT的潜在机制尚未完全了解。在此，我们证明αvβ3整合素诱导部分EMT，其特征是在保留上皮标志物的同时获得间充质表型。我们发现αvβ3整合素与肺腺癌患者的不良生存相关。此外，αvβ3整合素诱导的部分EMT以不依赖TGF-β的方式促进肺癌细胞的迁移、侵袭、肿瘤发生、干性和转移。此外，TGF-β1与αvβ3整合素协同促进EMT进程，而TGF-β信号抑制剂对αvβ3整合素诱导的部分EMT无影响。同时，微小RNA-200家族通过抑制αvβ3整合素细胞表面表达消除了αvβ3整合素诱导的部分EMT。这些发现表明αvβ3整合素是部分EMT的关键诱导因子，并突出了癌症进展的新机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8126/8060333/399ecba0916a/42003_2021_2003_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8126/8060333/04a38c6cd14d/42003_2021_2003_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8126/8060333/937692e8486e/42003_2021_2003_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8126/8060333/2d9d531a0303/42003_2021_2003_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8126/8060333/752cb997f2da/42003_2021_2003_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8126/8060333/1ab339b6162a/42003_2021_2003_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8126/8060333/dd278c40932c/42003_2021_2003_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8126/8060333/3275b044b358/42003_2021_2003_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8126/8060333/399ecba0916a/42003_2021_2003_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8126/8060333/04a38c6cd14d/42003_2021_2003_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8126/8060333/937692e8486e/42003_2021_2003_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8126/8060333/2d9d531a0303/42003_2021_2003_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8126/8060333/752cb997f2da/42003_2021_2003_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8126/8060333/1ab339b6162a/42003_2021_2003_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8126/8060333/dd278c40932c/42003_2021_2003_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8126/8060333/3275b044b358/42003_2021_2003_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8126/8060333/399ecba0916a/42003_2021_2003_Fig8_HTML.jpg

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