Identification of the atypical cadherin FAT1 as a novel glypican-3 interacting protein in liver cancer cells.
Identification of the atypical cadherin FAT1 as a novel glypican-3 interacting protein in liver cancer cells.
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肝癌细胞中非典型钙粘蛋白 FAT1 鉴定为新型磷脂酰肌醇蛋白聚糖 3 相互作用蛋白
DOI：
10.1038/s41598-020-79524-3
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发表时间：
2021-01-08
影响因子：
4.6
通讯作者：
Ho M
中科院分区：
文献类型：
--
作者：
Meng P;Zhang YF;Zhang W;Chen X;Xu T;Hu S;Liang X;Feng M;Yang X;Ho M
Glypican-3 （GPC3）是一种细胞表面硫酸肝素蛋白多糖，正在被评估为肝细胞癌（HCC）的新兴治疗靶点。GPC3已被证明与几种细胞外信号分子相互作用，包括Wnt、HGF和Hedgehog。在这里，我们报道了一个细胞表面跨膜蛋白（FAT1）作为一个新的GPC3相互作用蛋白。FAT1上的GPC3结合区域最初被定位到c端区域（Q14517，残基3662-4181），该区域覆盖了一个假定的受体酪氨酸磷酸酶（RTP）样结构域，一个层粘连蛋白g样结构域和五个egf样结构域。ELISA和流式细胞术精细定位显示，后4个egf样结构域（残基4013-4181）含有特异性GPC3结合位点，而RTP结构域（残基3662-3788）和下游层粘连蛋白g -2 egf样区域（残基3829-4050）具有非特异性GPC3结合位点。GPC3和FAT1同时或以相似的模式表现出相互作用，例如在HCC细胞中表达升高，在缺氧条件下表达上调，并且能够调节emt相关基因Snail、Vimentin和E-Cadherin的表达，促进HCC细胞迁移。综上所述，我们的研究为GPC3和FAT1促进HCC细胞迁移的新机制提供了初步证据。
Glypican-3 (GPC3) is a cell surface heparan sulfate proteoglycan that is being evaluated as an emerging therapeutic target in hepatocellular carcinoma (HCC). GPC3 has been shown to interact with several extracellular signaling molecules, including Wnt, HGF, and Hedgehog. Here, we reported a cell surface transmembrane protein (FAT1) as a new GPC3 interacting protein. The GPC3 binding region on FAT1 was initially mapped to the C-terminal region (Q14517, residues 3662-4181), which covered a putative receptor tyrosine phosphatase (RTP)-like domain, a Laminin G-like domain, and five EGF-like domains. Fine mapping by ELISA and flow cytometry showed that the last four EGF-like domains (residues 4013-4181) contained a specific GPC3 binding site, whereas the RTP domain (residues 3662-3788) and the downstream Laminin G-2nd EGF-like region (residues 3829-4050) had non-specific GPC3 binding. In support of their interaction, GPC3 and FAT1 behaved concomitantly or at a similar pattern, e.g. having elevated expression in HCC cells, being up-regulated under hypoxia conditions, and being able to regulate the expression of EMT-related genes Snail, Vimentin, and E-Cadherin and promoting HCC cell migration. Taken together, our study provides the initial evidence for the novel mechanism of GPC3 and FAT1 in promoting HCC cell migration.
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影响因子：
3.7
作者：
Gao W;Kim H;Ho M
通讯作者：
Ho M
人类抗体对Wnt信号的失活，该抗体识别肝癌治疗的Glypican-3硫酸盐链。
影响因子：
13.5
作者：
Gao, Wei;Kim, Heungnam;Feng, Mingqian;Phung, Yen;Xavier, Charles P.;Rubin, Jeffrey S.;Ho, Mitchell
通讯作者：
Ho, Mitchell
影响因子：
4.6
作者：
Gao W;Xu Y;Liu J;Ho M
通讯作者：
Ho M
影响因子：
8
作者：
Ahmed, Abdulrzag F.;de Bock, Charles E.;Thorne, Rick F.
通讯作者：
Thorne, Rick F.
影响因子：
64.5
作者：
Dong, Jixin;Feldmann, Georg;Pan, Duojia
通讯作者：
Pan, Duojia