STM:抑制Rac1b分子可能阻止早期肺癌发展为晚期肺癌

2012-07-16 ZinFingerNase 生物谷

美国佛罗里达州梅约诊所(Mayo Clinic)研究员说,被认为只在晚期癌症中发生的有助于肿瘤扩散的细胞变化也在早期肺癌中发生,并以此作为一种绕过生长控制的手段。相关研究结果于2012年7月11日发表在Science Translational Medicine期刊上。这一发现代表着人们对肺癌---可能很多其他类型的肿瘤---在疾病发生早期经历的转化程度产生新的认识。他们补充道,这一发现也指出一种

美国佛罗里达州梅约诊所(Mayo Clinic)研究员说,被认为只在晚期癌症中发生的有助于肿瘤扩散的细胞变化也在早期肺癌中发生,并以此作为一种绕过生长控制的手段。相关研究结果于2012年7月11日发表在Science Translational Medicine期刊上。这一发现代表着人们对肺癌---可能很多其他类型的肿瘤---在疾病发生早期经历的转化程度产生新的认识。他们补充道,这一发现也指出一种潜在的策略来阻止这种被称作上皮-间质转化(epithelial-mesenchymal transition, EMT)的过程。

论文通信作者、癌症生物学家Derek Radisky博士说,他们的研究指出在肺癌发展的最初阶段,EMT是肺癌转移过程中关键性的一步,并且发现早期肺癌细胞开启EMT以便绕过对正常细胞对异常细胞分裂的控制。

Radisky博士说,这一发现可能提供了一种新的方法来阻止早期肺癌发展为晚期肺癌,而且这种方法可能是通过抑制一种特定的分子Rac1b来实现的。

因为EMT是大家公认的在所有类型的实体瘤转化为晚期癌症过程中发生的,所以研究人员说,他们相信他们发现早期肺癌利用EMT也可能在其他癌症中发生。晚期癌症利用EMT将肿瘤细胞转变为一种能够在血液中迁移中的细胞类型。

Radisky博士说,这项研究提供巨大的新线索,从而有助于人们开发出新方法来尽可能早地治疗肺癌和其他癌症。

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.

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    2012-09-21 gdsun
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