在日前在线出版的《自然·细胞生物学》期刊上，科学家们报告说，他们鉴别出导致一种特殊进展性乳腺癌形成的因子。在炎性乳腺癌患者体内，一种蛋白质调控子的过多出现诱导了某种细胞黏滞因子出现。这些因子会将细胞转变为转移瘤。新发现有助于研制新的靶向疗法，阻止这种类型的癌症的扩散。
由于扩散速度快速，炎性乳腺癌是一种最为致命的乳腺癌症。Robert Schneider和同事的研究显示，炎性乳腺癌的特征之一是一种名为eIF4GI的蛋白质的过度表达。他们发现，尽管这种因子不会影响全部蛋白质的产出，但它会导致细胞黏滞调控子E-cadherin和连环蛋白p120ctn的增加，它们让癌细胞聚成团簇而不是附着在附近的细胞上。这些癌细胞团簇进入循环系统，并通过一种被动转移过程扩散到身体各组织，最终导致炎性乳腺癌的发生。对癌症模型小鼠的实验显示，遏制eIF4GI、E-cadherin或p120ctn的活性，均能破坏肿瘤的生长和入侵。作者指出，eIF4GI在乳腺癌中的作用依赖于p120ctn调控的松懈。
以炎性乳腺癌的导致分子为靶标，有助于开发治疗型干扰术，阻止这种特殊进展性乳腺癌的扩散。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Cell Biology 11, 903 - 908 (2009) 14 June 2009 | doi:10.1038/ncb1900
Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer
Deborah Silvera1, Rezina Arju1, Farbod Darvishian2, Paul H. Levine3, Ladan Zolfaghari3, Judith Goldberg4, Tsivia Hochman4, Silvia C. Formenti5,6 & Robert J. Schneider1,6
Inflammatory breast cancer (IBC) is the most lethal form of primary breast cancer1. IBC lethality derives from generation of tumour emboli, which are non-adherent cell clusters that rapidly spread by a form of continuous invasion known as passive metastasis2, 3, 4, 5. In most cancers, expression of E-cadherin, an epithelial marker, is indicative of low metastatic potential6, 7. In IBC, E-cadherin is overexpressed8 and supports formation of tumour emboli by promoting tumour cell interactions rather than adherence to stroma2, 3, 9. E-cadherin, a surface component of adherens junctions, is anchored by interaction with p120 catenin (p120). We show that the unique pathogenic properties of IBC result in part from overexpression of the translation initiation factor eIF4GI in most IBCs. eIF4GI reprograms the protein synthetic machinery for increased translation of mRNAs with internal ribosome entry sites (IRESs) that promote IBC tumour cell survival and formation of tumour emboli. Overexpression of eIF4GI promotes formation of IBC tumour emboli by enhancing translation of IRES-containing p120 mRNAs. These findings provide a new understanding of translational control in the development of advanced breast cancer.
1 Department of Microbiology New York University School of Medicine, New York, New York, 10016, USA.
2 Department of Pathology, New York University School of Medicine, New York, New York, 10016, USA.
3 George Washington University School of Public Health, Washington, District of Columbia, 20037, USA.
4 Department of Environmental Medicine, Division of Biostatistics, New York, New York, 10016, USA.
5 Department of Radiation Oncology New York, New York, 10016, USA.
6 NYU Cancer Institute, New York University School of Medicine, New York, New York, 10016, USA.
