2014年1月17日訊 /生物谷BIOON/--近日，Cleveland診所和Case Western Reserve School of Medicine一組研究人員確定了參與致命「三陰性」乳腺癌（TNBC）轉移的非常重要的複雜機制。
「三陰性」乳腺癌是非常難以治療的，病情會經常復發，是乳腺癌中最積極的形式。這一關鍵機制的發現可用於開發新的拯救患者生命的治療方式。Khalid Sossey-Alaoui博士說：10年前，研究團隊已經描述這些關鍵蛋白質的重要機制。
在三陰乳腺癌致命轉移中，研究人員關注兩種蛋白質，WAVE3和TGF-β，當兩種蛋白質結合在一起時，會促進腫瘤惡化。這是第一次，有研究發現這兩種蛋白之間的相互作用。
在研究過程中，下一步是要找到一種方法來傳遞抑制劑至腫瘤部位。利用納米粒子，Sossey-Alaoui團隊希望能直接靶向治療腫瘤部位和逆轉病情。他們的目標是在未來三年推動這一基礎研究進入臨床試驗。
這一發現有助於揭開導致轉移的複雜級聯事件，Stanton Gerson醫學博士解釋：轉移是一個複雜的多階段過程，其中原發腫瘤細胞侵入周圍的細胞，組織和器官，進入到血管，生存和轉移至身體其他部位。（生物谷Bioon.com）
Upregulated WAVE3 expression is essential for TGF-β-mediated EMT and metastasis of triple-negative breast cancer cells
Molly A. Taylor, Gangarao Davuluri, Jenny G. Parvani, Barbara J. Schiemann, Michael K. Wendt, Edward F. Plow, William P. Schiemann, Khalid Sossey-Alaoui
Breast cancer is the second leading cause of cancer death in women in the United States. Metastasis accounts for the death of ~90 % of these patients, yet the mechanisms underlying this event remain poorly defined. WAVE3 belongs to the WASP/WAVE family of actin-binding proteins that play essential roles in regulating cell morphology, actin polymerization, cytoskeleton remodeling, cell motility, and invasion. Accordingly, we demonstrated previously that WAVE3 promotes the acquisition of invasive and metastatic phenotypes by human breast cancers. Herein, we show that transforming growth factor-β (TGF-β) selectively and robustly induced the expression of WAVE3 in metastatic breast cancer cells, but not in their nonmetastatic counterparts. Moreover, the induction of WAVE3 expression in human and mouse triple-negative breast cancer cells (TNBCs) by TGF-β likely reflects its coupling to microRNA expression via a Smad2- and β3 integrin-dependent mechanism. We further demonstrate the requirement for WAVE3 expression in mediating the initiation of epithelial–mesenchymal transition (EMT) programs stimulated by TGF-β. Indeed, stable depletion of WAVE3 expression in human TNBC cells prevented TGF-β from inducing EMT programs and from stimulating the proliferation, migration, and the formation of lamellipodia in metastatic TNBC cells. Lastly, we observed WAVE3 deficiency to abrogate the outgrowth of TNBC cell organoids in 3-dimensional organotypic cultures as well as to decrease the growth and metastasis of 4T1 tumors produced in syngeneic Balb/C mice. Indeed, WAVE3 deficiency significantly reduced the presence of sarcomatoid morphologies indicative of EMT phenotypes in pulmonary TNBC tumors as compared to those detected in their parental counterparts. Collectively, these findings indicate the necessity for WAVE3 expression and activity during EMT programs stimulated by TGF-β; they also suggest that measures capable of inactivating WAVE3 may play a role in alleviating metastasis stimulated by TGF-β.