The membrane-bound and soluble form of melanotransferrin function independently in the diagnosis and targeted therapy of lung cancer.
The membrane-bound and soluble form of melanotransferrin function independently in the diagnosis and targeted therapy of lung cancer.
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膜结合形式和可溶形式的黑素转铁蛋白在肺癌的诊断和靶向治疗中独立发挥作用
DOI：
10.1038/s41419-020-03124-2
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发表时间：
2020-10-30
影响因子：
9
通讯作者：
He J
中科院分区：
文献类型：
--
作者：
Lei Y;Lu Z;Huang J;Zang R;Che Y;Mao S;Fang L;Liu C;Wang X;Zheng S;Sun N;He J
黑素转铁蛋白（Melanotransferrin，MFI 2）是一种新发现的肿瘤相关蛋白，由膜结合型（mMFI 2）和分泌型（sMFI 2）两种蛋白质组成。然而，关于其表达模式及其在肺癌中的相关性知之甚少。在这里，我们发现两种形式的MFI 2在肺癌中高度表达。应用公共数据库和qRT-PCR检测肺癌组织中MFI 2的表达。利用过表达和敲低表达的细胞系及重组sMFI 2蛋白研究mMFI 2和sMFI 2的功能。采用RNA-seq、蛋白质芯片、ChIP、免疫沉淀、ELISA和免疫荧光等方法研究mMFI 2和sMFI 2的分子生物学机制。我们发现mMFI 2通过下调转录因子KLI 4促进EMT共同标志物N-cadherin的表达，进而促进肿瘤转移; sMFI 2可以自分泌方式促进自体肿瘤细胞的转移，但机制与mMFI 2不同。此外，研究证实sMFI 2可抑制血管内皮细胞的迁移，并以旁分泌的方式增强血管生成反应。我们认为MFI 2的两种形式在肺癌中的表达和功能是相对独立的。mMFI 2是一个潜在的肺癌治疗靶点，而sMFI 2在晚期肺癌中高度富集，可作为肿瘤分期指标。
Melanotransferrin (MFI2) is a newly identified tumor-associated protein, which consists of two forms of proteins, membrane-bound (mMFI2) and secretory (sMFI2). However, little is known about the expression pattern and their relevance in lung cancer. Here, we found that both two forms of MFI2 are highly expressed in lung cancer. The expression of MFI2 in lung cancer was detected by using the public database and qRT-PCR. Overexpression and knockdown cell lines and recombinant sMFI2 protein were used to study the function of mMFI2 and sMFI2. RNA-seq, protein chip, ChIP assay, Immunoprecipitation, ELISA, and immunofluorescence were used to study the molecular biological mechanism of mMFI2 and sMFI2. We found that mMFI2 promoted the expression of EMT’s common marker N-cadherin by downregulating the transcription factor KLI4, which in turn promoted tumor metastasis; sMFI2 could promote the metastasis of autologous tumor cells in an autocrine manner but the mechanism is different from that of mMFI2. In addition, sMFI2 was proved could inhibit the migration of vascular endothelial cells and subsequently enhance angiogenic responses in a paracrine manner. We propose that the expressions and functions of the two forms of MFI2 in lung cancer are relatively independent. Specifically, mMFI2 was a potential lung cancer therapeutic target, while sMFI2 was highly enriched in advanced lung cancer, and could be used as a tumor staging index.
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影响因子：
4.7
作者：
Demeule, M;Poirier, J;Béliveau, R
通讯作者：
Béliveau, R
影响因子：
--
作者：
Kim, Jinkyung;Kang, Sung-Min;Hong, Su-Hyung
通讯作者：
Hong, Su-Hyung
一个独特的载体，用于在血脑屏障之外提供治疗化合物。
影响因子：
3.7
作者：
Karkan, Delara;Pfeifer, Cheryl;Vitalis, Timothy Z.;Arthur, Gavin;Ujiie, Maki;Chen, Qingqi;Tsai, Sam;Koliatis, Gerrasimo;Gabathuler, Reinhard;Jefferies, Wilfred A.
通讯作者：
Jefferies, Wilfred A.
影响因子：
8
作者：
Lorenzon, E.;Colladel, R.;Mongiat, M.
通讯作者：
Mongiat, M.
影响因子：
3.7
作者：
Rolland, Yanneve;Demeule, Michel;Beliveau, Richard
通讯作者：
Beliveau, Richard