肿瘤干细胞的耐药性是导致化疗失败的一个主要原因，深入探究调控肿瘤干细胞耐药的机制并成功逆转，将对提升化疗效果产生重要价值。本课题组前期发现，在头颈鳞癌中活化白细胞粘附分子（ALCAM）是肿瘤干细胞的相关分子，并能够维持EGFR-AKT信号通路的激活。研究还发现，过表达ALCAM能上调ABCB1转运体的表达，增强肿瘤干细胞对化疗药物的抵抗。目前ALCAM调控ABCB1转运体表达的具体分子机制以及抑制ALCAM是否能逆转耐药性尚不清楚。本课题拟通过扩大样本量，检测ALCAM蛋白与ABCB1转运体在头颈鳞癌化疗敏感和化疗耐药组织中的表达水平，分析确定ALCAM、ABCB1转运体与肿瘤耐药的相关性；体外探讨ALCAM-ABCB1信号轴在耐药性形成中的作用机制；肿瘤组织移植瘤模型，观察靶向干预ALCAM表达对肿瘤耐药性的逆转效果。研究将为明确ALCAM作为逆转化疗耐药的靶点提供理论依据和实验基础。

The chemotherapy resistance of cancer stem cells (CSCs) is the main reason for the failure therapy. It is of important to investigate the related mechnisms of chemotherapy resistance of CSCs. Our group has found that activated leukocyte cell adhesion molecule (ALCAM) is related with the stem of cancer cell, wich could sustain the activity of EGFR-AKT signaling pathway. The pre-experiment also showed that ALCAM could upregulate the expression of ABCB1 transport, thus enhancing chemotherapy resistance. The mechanisms that ALCAM regulate the expression of ABCB1 transport is not reported. In this study, we will detect the expression of ALCAM and ABCB1 in lots of tumor tissues from patients to analyse the relationship among ALCAM protein, ABCB1 transport and drug-resistance. We then investigate the related mechnisms that ALCAM regulates the expression of ABCB1 transport in vitro. At last, we would identify the potential value of ALCAM as the therapeutic target in vivo.