CD147通过RSK2调控细胞恶性转化及皮肤鳞癌的作用机制研究

Abstract: Primary cutaneous Squamous cell carcinoma (cSCC) , which causes the majority of deaths among the non-melanoma skin malignancies, is a malignant tumor that arises from the keratinizing cells of the epidermis. Our previous results showed that CD147 and RSK2 are over expressed in cSCC tissues, compared with that in normal skin tissues. So we proposed that CD147 could be a critical molecule in epithelial transformation and progress of cSCC through involving in RSK2-related pathway. First of all, we should clear the interaction between CD147 and RSK2, especially the influence of CD147 on RSK2 activation, using IP, pull down assay and western blot; Then we use squamous cancer cells and rat models, which have different expression level of CD147 / RSK2, to analyzed cells malignant transformation and squamous carcinoma proliferation, invasion and metastasis of malignant phenotype changes. That can explore the significance of CD147 / RSK2 interaction among them; At last, we will observe the expression and localization of CD147, RSK2 in squamous carcinoma tissues from clinical patients.This research will demonstrate the meaning of increased expression of CD147 in SCC and also provide a new perspective for the occurrence of cell malignant transformation and squamous cell carcinomas, invasion and metastasis mechanism.

皮肤鳞状细胞癌是一种致死率较高的非黑色素瘤皮肤恶性肿瘤。研究显示CD147及RSK2均在皮肤鳞癌中高表达，其具体机制不详。预实验结果证实CD147与RSK2存在相互作用。因此我们假设CD147通过RSK2影响RSK2下游信号通路从而介导上皮细胞恶性转化及鳞癌的发生发展。首先我们采用IP、pull down、IF的方法进一步明确CD147与RSK2的相互作用，尤其是对RSK2活化的影响；随后利用CD147/RSK2不同表达水平的鳞癌细胞株及鼠模型，分析其恶性转化及鳞癌增殖，侵袭转移等恶性表型的变化，深入探讨CD147/RSK2相互作用在其中的意义；在人鳞癌组织中观察两者的表达及定位，在临床上验证这一机制。本研究解答了CD147在SCC中增高表达的意义所在，为细胞恶性转化及鳞癌的发生、侵袭、转移的机制提供了新的视角。