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M Villa-Morales M A Cobos E González-Gugel V álvarez-Iglesias B Martínez M A Piris A Carracedo J Benítez J Fernández-Piqueras 《Cell death & disease》2014,5(3):e1110
The acquisition of resistance towards FAS-mediated apoptosis may be required for tumor formation. Tumors from various histological origins exhibit FAS mutations, the most frequent being hematological malignancies. However, data regarding FAS mutations or FAS signaling alterations are still lacking in precursor T-cell lymphoblastic lymphomas (T-LBLs). The available data on acute lymphoblastic leukemia, of precursor origin as well, indicate a low frequency of FAS mutations but often report a serious reduction in FAS-mediated apoptosis as well as chemoresistance, thus suggesting the occurrence of mechanisms able to deregulate the FAS signaling pathway, different from FAS mutation. Our aim at this study was to determine whether FAS-mediated apoptotic signaling is compromised in human T-LBL samples and the mechanisms involved. This study on 26 T-LBL samples confirms that the FAS system is impaired to a wide extent in these tumors, with 57.7% of the cases presenting any alteration of the pathway. A variety of mechanisms seems to be involved in such alteration, in order of frequency the downregulation of FAS, the deregulation of other members of the pathway and the occurrence of mutations at FAS. Considering these results together, it seems plausible to think of a cumulative effect of several alterations in each T-LBL, which in turn may result in FAS/FASLG system deregulation. Since defective FAS signaling may render the T-LBL tumor cells resistant to apoptotic cell death, the correct prognosis, diagnosis and thus the success of anticancer therapy may require such an in-depth knowledge of the complete scenario of FAS-signaling alterations. 相似文献
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Functional Polymorphisms in FAS/FASL System Increase the Risk of Neuroblastoma in Chinese Population
Wei Han Yuling Zhou Rong Zhong Chen Wu Ranran Song Li Liu Li Zou Yan Qiao Kan Zhai Jiang Chang Liming Huang Li Liu Xuzai Lu Jiao Lou Dianke Yu Wen Tan Jinzhe Zhang Huanmin Wang Xiaoping Miao 《PloS one》2013,8(8)
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