FHOD1, a formin upregulated in epithelial-mesenchymal transition, participates in cancer cell migration and invasion.
FHOD1, a formin upregulated in epithelial-mesenchymal transition, participates in cancer cell migration and invasion.
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DOI：
10.1371/journal.pone.0074923
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Carpén O
中科院分区：
文献类型：
--
作者：
Gardberg M;Kaipio K;Lehtinen L;Mikkonen P;Heuser VD;Talvinen K;Iljin K;Kampf C;Uhlen M;Grénman R;Koivisto M;Carpén O
癌细胞可以通过上皮-间质转化（epithelial-to-mesenchymal transition， EMT）获得侵袭和转移能力。利用这种细胞可塑性机制，恶性细胞可以重塑其肌动蛋白骨架并下调细胞间接触所需的蛋白质。细胞骨架重组导致间充质形态和侵袭潜力增加的机制尚不清楚。肌动蛋白成核形成蛋白被认为是EMT的关键参与者。在这里，我们分析了哪些formmins在鳞状细胞癌相关的EMT中发生了改变。FHOD1是一种研究较少的双胍，在EMT中表现出明显的上调。在人体组织中，FHOD1主要在间充质细胞中表达，在上皮细胞中表达较少。然而，口腔鳞状细胞癌的标本在侵袭边缘的间充质转化细胞中显示出一致的FHOD1上调。这种上调在口腔鳞癌模型中得到证实，在EMT后，FHOD1的表达以PI3K信号依赖的方式显著增加。在EMT细胞中，FHOD1参与梭形形态和间质f -肌动蛋白组织。此外，功能分析表明，FHOD1有助于细胞迁移和侵袭。最后，FHOD1缺失降低了EMT癌细胞形成侵过体和降解细胞外基质的能力。我们的研究结果表明，FHOD1参与了EMT的细胞骨架变化。此外，我们发现FHOD1上调发生在体内癌细胞EMT过程中，这表明FHOD1可能有助于肿瘤进展。
Cancer cells can obtain their ability to invade and metastasise by undergoing epithelial-to-mesenchymal transition (EMT). Exploiting this mechanism of cellular plasticity, malignant cells can remodel their actin cytoskeleton and down-regulate proteins needed for cell-cell contacts. The mechanisms of cytoskeletal reorganisation resulting in mesenchymal morphology and increased invasive potential are poorly understood. Actin nucleating formins have been implicated as key players in EMT. Here, we analysed which formins are altered in squamous cell carcinoma related EMT. FHOD1, a poorly studied formin, appeared to be markedly upregulated upon EMT. In human tissues FHOD1 was primarily expressed in mesenchymal cells, with little expression in epithelia. However, specimens from oral squamous cell cancers demonstrated consistent FHOD1 upregulation in mesenchymally transformed cells at the invasive edge. This upregulation was confirmed in an oral squamous carcinoma model, where FHOD1 expression was markedly increased upon EMT in a PI3K signalling dependent manner. In the EMT cells FHOD1 contributed to the spindle-shaped morphology and mesenchymal F-actin organization. Furthermore, functional assays demonstrated that FHOD1 contributes to cell migration and invasion. Finally, FHOD1 depletion reduced the ability of EMT cancer cells to form invadopodia and to degrade extracellular matrix. Our results indicate that FHOD1 participates in cytoskeletal changes in EMT. In addition, we show that FHOD1 upregulation occurs during cancer cell EMT in vivo, which indicates that FHOD1 may contribute to tumour progression.
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DOI：
10.1186/1478-811x-8-23
发表时间：
2010-09-07
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Parri M;Chiarugi P
通讯作者：
Chiarugi P
影响因子：
3.2
作者：
Takkunen, Minna;Grenman, Reidar;Virtanen, Ismo
通讯作者：
Virtanen, Ismo
影响因子：
4
作者：
Koka, S;Neudauer, CL;Westendorf, JJ
通讯作者：
Westendorf, JJ
影响因子：
12.3
作者：
Kilpinen, Sami;Autio, Reija;Ojala, Kalle;Iljin, Kristiina;Bucher, Elmar;Sara, Henri;Pisto, Tommi;Saarela, Matti;Skotheim, Rolf I.;Bjorkman, Mari;Mpindi, John-Patrick;Haapa-Paananen, Saija;Vainio, Paula;Edgren, Henrik;Wolf, Maija;Astola, Jaakko;Nees, Matthias;Hautaniemi, Sampsa;Kallioniemi, Olli
通讯作者：
Kallioniemi, Olli
影响因子：
--
作者：
Gardberg M;Talvinen K;Kaipio K;Iljin K;Kampf C;Uhlen M;Carpén O
通讯作者：
Carpén O