α-Catulin marks the invasion front of squamous cell carcinoma and is important for tumor cell metastasis.
α-Catulin marks the invasion front of squamous cell carcinoma and is important for tumor cell metastasis.
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DOI：
10.1158/1541-7786.mcr-12-0169
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发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
Kobielak A
中科院分区：
文献类型：
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作者：
Cao C;Chen Y;Masood R;Sinha UK;Kobielak A
鳞状细胞癌包括最常见的人类上皮癌类型。头颈部鳞状细胞癌（HNSCC）是一种侵袭性很强的癌症，由于诊断晚和淋巴结转移，预后很差。在所有涉及癌变的过程中，局部侵袭和远处转移在临床上是最相关的，但在分子水平上是最不清楚的。我们发现，在体内，α-catenin同源物- α-catulin，一种最初报道与Lbc Rho鸟嘌呤核苷酸交换因子相互作用的蛋白质，在恶性人类HNSCC和小鼠口腔SCC模型中的肿瘤侵袭前沿和转移细胞流中高度表达。hHNSCC细胞系中α-catulin的敲低显著降低了这些细胞在体外的迁移和侵袭潜力以及在体内异种移植物中的转移潜力。对缺乏α-卡图林的肿瘤的分析表明，肿瘤细胞不能侵入周围的基质。因此，这些肿瘤的转录谱显示，α-catulin消融伴随着参与细胞迁移和侵袭的基因的变化。有趣的是，体外实验表明α-卡图林表达的上调与肿瘤细胞从上皮向间充质形态的转变以及EMT标志物波形蛋白和snail的上调相关。总体而言，这些结果强烈表明α-卡图林有助于转移细胞的侵袭行为，并可用作癌症患者的预后标志物和未来的治疗靶点。
Squamous cell cancers comprise the most common types of human epithelial cancers. One subtype, head and neck squamous cell carcinoma (HNSCC), is a particularly aggressive cancer with poor prognosis due to late diagnosis and lymph node metastasis. Of all the processes involved in carcinogenesis, local invasion and distant metastasis are clinically the most relevant, but are the least well understood on a molecular level. Here we find that in vivo, the α-catenin homologue – α-catulin, a protein originally reported to interact with Lbc Rho guanine nucleotide exchange factor, is highly expressed at the tumor invasion front and in the metastatic streams of cells in both malignant human HNSCCs and a mouse model of oral SCC. Knockdown of α-catulin in hHNSCC cell lines dramatically decrease the migratory and invasive potential of those cells in vitro and metastatic potential in xenotransplants in vivo. Analysis of tumors deficient in α-catulin showed that the tumor cells are unable to invade the surrounding stroma. Accordingly, transcriptional profiling of those tumors revealed that α-catulin ablation is accompanied by changes in genes involved in cell migration and invasion. Interestingly enough, in vitro experiments show that an upregulation of α-catulin expression correlates with the transition of tumor cells from an epithelial to a mesenchymal morphology, as well as an upregulation of EMT markers vimentin and snail. Overall, these results strongly indicate that α-catulin contributes to the invasive behavior of metastatic cells, and may be used as a prognostic marker and future therapeutic target for cancer patients.