c-FLIP入核在乳腺癌转移及耐药中的作用及分子机制

作为女性最常见的恶性肿瘤之一，乳腺癌的转移是患者死亡最主要的原因，因此控制转移是临床治疗最大的挑战，其背后的机制研究尤为重要。c-FLIP是一个重要的抗凋亡蛋白，可以抑制TRAIL诱导的凋亡，在包括乳腺癌在内的多种肿瘤细胞中高表达，与肿瘤的凋亡抵抗密切相关。c-FLIP在胞浆与胞核均有分布，胞核中的c-FLIP能增强c-Jun和Wnt-β-catenin下游靶基因的转录,与anti-Fas(CH-11)诱导细胞死亡相关。我们的研究表明c-FLIP通过调节N-Cadherin和Snail的表达参与非小细胞肺癌的EMT过程；该项目已发现c-FLIP主要定位在乳腺癌细胞的胞核中，我们将继续研究定位于胞核的c-FLIP与乳腺癌细胞的侵袭转移之间的关系，并通过研究c-FLIP入核后引起基因转录水平的变化，确定c-FLIP调节的关键靶分子，探讨c-FLIP调控乳腺癌细胞侵袭转移的分子机制。

Breast carcinoma is one of the most common malignancy in women, Metastasis is responsible for mortality in breast cancer patients. Fighting metastasis is a major challenge in clinical cancer therapy, researching the underlying mechanisms is particularly important. Cellular FLICE-inhibitory protein (c-FLIP) is a major anti-apoptotic protein that inhibits TRAIL-induced apoptosis in malignant cells. c-FLIP is high expressed in a variety of tumor cells including breast cancer, and is closely related to the apoptosis resistance of tumor. c-FLIP localizes in both the nucleus and cytoplasm. Nuclear c-FLIP can enhance the transcription of c-Jun and Wnt-beta-catenin downstream target genes, and involved in anti-Fas (CH-11) induced cell death. Our research shows that c-FLIP promoting the EMT of NSCLC cells by up-regulating N-Cadherin and Snail expression. Our preliminary research indicates that c-FLIP localizes in both the nucleus and cytoplasm in breast cancer cells. This subject will study the relationship between nuclear c-FLIP and the invasion and metastasis of breast cancer cells, search for the key target molecules of c-FLIP in this process by the analysis of changing in gene transcription.