FAD104, a regulator of adipogenesis, is a novel suppressor of TGF-β-mediated EMT in cervical cancer cells.
FAD104, a regulator of adipogenesis, is a novel suppressor of TGF-β-mediated EMT in cervical cancer cells.
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DOI：
10.1038/s41598-017-16555-3
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发表时间：
2017-11-27
影响因子：
4.6
通讯作者：
Nishizuka M
中科院分区：
文献类型：
--
作者：
Goto M;Osada S;Imagawa M;Nishizuka M
上皮向间充质转化(EMT)是上皮细胞转化为具有侵袭能力的间充质表型的生物学过程，有助于肿瘤的进展、转移和获得化疗耐药。为了寻找新的肿瘤治疗靶点，阐明EMT诱导的分子机制是很重要的。我们之前已经报道，脂肪细胞分化的正向调节因子Fad104抑制黑色素瘤和乳腺癌细胞的侵袭和转移。在这项研究中，我们发现FAD104作为一种新的转化生长因子-β(转化生长因子-β)介导的宫颈癌细胞内皮细胞转移的抑制因子。FAD104在转化生长因子-β介导的人宫颈癌HeLa细胞EMT过程中表达上调。Fad104的表达下调增强了转化生长因子-β介导的细胞内膜转移和迁移。反之，FAD104的过表达抑制了转化生长因子-β诱导的血管内皮细胞转化。此外，我们还发现FAD104通过转化生长因子-β负向调节Smad2和Smad3的磷酸化，而正向调节Smad1/5/8的磷酸化。这些发现表明，FAD104是一种新的转化生长因子-β信号转导抑制因子，并抑制转化生长因子-β介导的宫颈癌细胞转分化。
Epithelial-to-mesenchymal transition (EMT) is a biological process in which epithelial cells translate into a mesenchymal phenotype with invasive capacities, contributing to tumour progression, metastasis, and the acquisition of chemotherapy resistance. To identify new therapeutic targets for cancers, it is important to clarify the molecular mechanism of induction of EMT. We have previously reported that fad104, a positive regulator of adipocyte differentiation, suppressed the invasion and metastasis of melanoma and breast cancer cells. In this study, we showed that FAD104 functions as a novel suppressor of transforming growth factor-β (TGF-β)–mediated EMT in cervical cancer cells. Expression of FAD104 is upregulated during TGF-β–mediated EMT in human cervical cancer HeLa cells. Reduction of fad104 expression enhanced TGF-β–mediated EMT and migration in HeLa cells. Conversely, overexpression of FAD104 suppressed TGF-β–induced EMT. In addition, we showed that FAD104 negatively regulated phosphorylation of Smad2 and Smad3 but positively regulated phosphorylation of Smad1/5/8 via treatment with TGF-β. These findings demonstrate that FAD104 is a novel suppressor of TGF-β signalling and represses TGF-β–mediated EMT in cervical cancer cells.
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DOI：
10.1016/j.bbrc.2010.05.077
发表时间：
2010-06-25
影响因子：
3.1
作者：
Kishimoto, Keishi;Kato, Ayumi;Imagawa, Masayoshi
通讯作者：
Imagawa, Masayoshi
影响因子：
16
作者：
Goumans, MJ;Valdimarsdottir, G;ten Dijke, P
通讯作者：
ten Dijke, P
影响因子：
56.9
作者：
Lovchinsky, I.;Sushkov, A. O.;Lukin, M. D.
通讯作者：
Lukin, M. D.
影响因子：
4.8
作者：
Cao, Ying;Szabolcs, Annamaria;Mukhopadhyay, Debabrata
通讯作者：
Mukhopadhyay, Debabrata
影响因子：
64.8
作者：
Fischer KR;Durrans A;Lee S;Sheng J;Li F;Wong ST;Choi H;El Rayes T;Ryu S;Troeger J;Schwabe RF;Vahdat LT;Altorki NK;Mittal V;Gao D
通讯作者：
Gao D