2014年8月29日 訊 /生物谷BIOON/ --近日，刊登在國際雜誌Molecular and Cellular Biology上的一篇研究論文中，來自麥基爾大學的研究人員通過研究表明，一種名為p66ShcA的蛋白質或許可以作為一種生物標記物來幫助鑑別乳腺癌患者的預後不良。
在乳腺癌中，一種名為上皮細胞向間充質細胞轉分化(epithelial to mesenchymal transition，EMT)的過程可以幫助乳腺癌轉移；上皮細胞系的表面同環境可以直接接觸，比如皮膚和胃腸道，而間充質細胞則是胚胎組織和結締組織中的一種細胞，細胞間可以形成鬆散的結構。腫瘤細胞會失去發育成表皮細胞的特性，比如吸附的特性等，但其可以獲得更多的間充質細胞，這就使得腫瘤細胞可以遷移到更遠的器官或組織中去。
這項研究中，研究者Josie Ursini-Siegel表示，我們在乳腺癌組織發現了一種名為p66ShcA的蛋白質，其可以經歷EMT過程；在乳腺癌亞型中，p66ShcA表達水平的升高和大量上皮細胞向間質細胞過度相關基因的表達直接相關，而p66ShcA或許可以作為一種預後生物標記物來幫助鑑別乳腺癌患者預後情況。
預測癌症患者的預後情況對於管理療法非常重要，預後良好的患者可以免去更具攻擊性的療法，乳腺癌分為至少5個亞型，每一種都會給患者帶來不同的結果；儘管如此，早期研究揭示在不同亞型的乳腺癌中存在一定的異質性，這就使得對不同乳腺癌患者預後評估變得更加困難。
最後研究者說道，通過揭示引發腫瘤異質性及癌轉移的戒指，包括EMT過程，或許幫助科學家們開發治療或者改善患者預後的新型療法。（生物谷Bioon.com）
p66ShcA Promotes Breast Cancer Plasticity by Inducing an Epithelial to Mesenchymal Transition
Jesse Hudson1, Jacqueline R. Ha1, Valerie Sabourin1, Ryuhjin Ahn1, Rachel La Selva1, Julie Livingstone2, Lauren Podmore1, Jennifer Knight2, Laura Forrest1,2, Nicole Beauchemin2,3,4, Michael Hallett2,4, Morag Park2,3,4 and Josie Ursini-Siegel1,3#
Breast cancers are stratified into distinct subtypes, which influence therapeutic responsiveness and patient outcome. Patients with luminal breast cancers are often associated with a better prognosis relative to other subtypes. However, subsets of patients with luminal disease remain at increased risk of cancer-related death. A critical process that increases the malignant potential of breast cancers is the epithelial-to-mesenchymal transition (EMT). The p66ShcA adaptor protein stimulates the formation of reactive oxygen species in response to stress stimuli. In this study, we report a novel role for p66ShcA in inducing an EMT in HER2+ luminal breast cancers. p66ShcA increases the migratory properties of breast cancer cells and enhances signaling downstream of the Met receptor tyrosine kinase in these tumors. Moreover, Met activation is required for a p66ShcA-induced EMT in luminal breast cancer cells. Finally, elevated p66ShcA levels are associated with the acquisition of an EMT in primary breast cancers spanning all molecular subtypes, including luminal tumors. This is of high clinical relevance as the luminal and HER2 subtypes, together, comprise 80% of all newly diagnosed breast cancers. This study identifies p66ShcA as one of the first prognostic biomarkers for the identification of more aggressive tumors with mesenchymal properties, regardless of molecular subtype.