上皮癌特指來(lái)源于外胚層和內(nèi)胚層,，發(fā)生于上皮細(xì)胞的惡性腫瘤,。鱗狀細(xì)胞癌（SCC）是人上皮癌最常見(jiàn)的類(lèi)型之一。其中頭部和頸部鱗狀細(xì)胞癌（HNSCC）,，由于后期診斷死亡率居高不下,，淋巴結(jié)轉(zhuǎn)移的預(yù)后差，是一種最具侵略性的癌癥類(lèi)型,。
所有癌癥過(guò)程的發(fā)生,，都涉及到局部侵襲和遠(yuǎn)端器官轉(zhuǎn)移，而這兩者與臨床上腫瘤患者的生存最相關(guān),，但至于腫瘤侵襲轉(zhuǎn)移的分子機(jī)制一直得不到良好的解釋,。
在Molecular Cancer Research雜志上的一篇研究論文中，研究人員發(fā)現(xiàn)體內(nèi)蛋白質(zhì)α-連環(huán)蛋白的同源類(lèi)型物α-catulin的在腫瘤的侵襲轉(zhuǎn)移過(guò)程中發(fā)揮重要調(diào)節(jié)作用,。敲除hHNSCC細(xì)胞株的alpha-catulin后,，這些細(xì)胞在體外和轉(zhuǎn)移性在體內(nèi)的遷移和侵襲潛力大大降低。腫瘤α-catulin表達(dá)缺失實(shí)驗(yàn)分析表明,，α-catulin抑制后腫瘤細(xì)胞是無(wú)法侵入周?chē)|(zhì)的,。
而
腫瘤轉(zhuǎn)錄基因譜研究顯示，α-catulin的消融伴隨著細(xì)胞遷移和侵襲的基因變化,。有趣的是,，體外實(shí)驗(yàn)表明，α-catulin表達(dá)的上調(diào)與上皮腫瘤細(xì)胞間質(zhì)形態(tài)轉(zhuǎn)變,，以及上皮細(xì)胞間質(zhì)轉(zhuǎn)型（EMT）的標(biāo)記物波形蛋白,、snail的上調(diào)呈相關(guān)性。總的來(lái)說(shuō),，研究結(jié)果強(qiáng)烈表明α-catulin有助于轉(zhuǎn)移性細(xì)胞的侵襲,，可作為癌癥患者的預(yù)后指標(biāo)和治療策略。（生物谷：Bioon.com）
doi:10.1158/1541-7786.MCR-12-0169
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α-catulin marks the invasion front of squamous cell carcinoma and is important for tumor cell metastasis.
Christine Cao, Yibu Chen, Rizwan Massod, Uttam K Sinha, and Agnieszka Kobielak*
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.
