美國(guó)佛羅里達(dá)州梅約診所(Mayo Clinic)研究員說(shuō),，被認(rèn)為只在晚期癌癥中發(fā)生的有助于腫瘤擴(kuò)散的細(xì)胞變化也在早期肺癌中發(fā)生，并以此作為一種繞過(guò)生長(zhǎng)控制的手段,。相關(guān)研究結(jié)果于2012年7月11日發(fā)表在Science Translational Medicine期刊上。這一發(fā)現(xiàn)代表著人們對(duì)肺癌---可能很多其他類型的腫瘤---在疾病發(fā)生早期經(jīng)歷的轉(zhuǎn)化程度產(chǎn)生新的認(rèn)識(shí)。他們補(bǔ)充道,，這一發(fā)現(xiàn)也指出一種潛在的策略來(lái)阻止這種被稱作上皮-間質(zhì)轉(zhuǎn)化(epithelial-mesenchymal transition, EMT)的過(guò)程,。
論文通信作者、癌癥生物學(xué)家Derek Radisky博士說(shuō),，他們的研究指出在肺癌發(fā)展的最初階段,，EMT是肺癌轉(zhuǎn)移過(guò)程中關(guān)鍵性的一步，并且發(fā)現(xiàn)早期肺癌細(xì)胞開(kāi)啟EMT以便繞過(guò)對(duì)正常細(xì)胞對(duì)異常細(xì)胞分裂的控制,。
Radisky博士說(shuō),，這一發(fā)現(xiàn)可能提供了一種新的方法來(lái)阻止早期肺癌發(fā)展為晚期肺癌，而且這種方法可能是通過(guò)抑制一種特定的分子Rac1b來(lái)實(shí)現(xiàn)的,。
因?yàn)镋MT是大家公認(rèn)的在所有類型的實(shí)體瘤轉(zhuǎn)化為晚期癌癥過(guò)程中發(fā)生的,，所以研究人員說(shuō)，他們相信他們發(fā)現(xiàn)早期肺癌利用EMT也可能在其他癌癥中發(fā)生,。晚期癌癥利用EMT將腫瘤細(xì)胞轉(zhuǎn)變?yōu)橐环N能夠在血液中遷移中的細(xì)胞類型,。
Radisky博士說(shuō)，這項(xiàng)研究提供巨大的新線索,，從而有助于人們開(kāi)發(fā)出新方法來(lái)盡可能早地治療肺癌和其他癌癥,。(生物谷：Bioon.com)
doi: 10.1126/scitranslmed.3004062
PMC:
PMID:
Matrix Metalloproteinase Induction of Rac1b, a Key Effector of Lung Cancer Progression
Melody L. Stallings-Mann1,*, Jens Waldmann1,2, Ying Zhang1, Erin Miller1, Mona L. Gauthier3, Daniel W. Visscher4, Gregory P. Downey5,6,7, Evette S. Radisky1, Alan P. Fields1 and Derek C. Radisky
Lung cancer is more deadly than colon, breast, and prostate cancers combined, and treatment improvements have failed to improve prognosis significantly. Here, we identify a critical mediator of lung cancer progression, Rac1b, a tumor-associated protein with cell-transforming properties that are linked to the matrix metalloproteinase (MMP)–induced epithelial-mesenchymal transition (EMT) in lung epithelial cells. We show that expression of mouse Rac1b in lung epithelial cells of transgenic mice stimulated EMT and spontaneous tumor development and that activation of EMT by MMP-induced expression of Rac1b gave rise to lung adenocarcinoma in the transgenic mice through bypassing oncogene-induced senescence. Rac1b is expressed abundantly in stages 1 and 2 of human lung adenocarcinomas and, hence, is an attractive molecular target for the development of new therapies that prevent progression to later-stage lung cancers.
