我们以往的实验结果表明，LOXL2（赖氨酰氧化酶样蛋白2）在食管癌中显著异常过表达，是一重要食管癌功能基因，与癌细胞的侵袭移动、淋巴结转移相关，与癌细胞的分裂增殖无关。最近，我们在食管癌中发现了LOXL2的一个新剪接亚型，因外显子13剪接缺失，被命名为L2Δ13。进一步的实验结果表明，与LOXL2原型相比，L2Δ13的酶活性极显著降低，且滞留于细胞浆；令人意外的是，除了促食管癌细胞侵袭移动能力变得更强外，L2Δ13还新增了十分明显的促食管癌细胞分裂增殖新功能，但分子作用机制如何这一重要科学问题尚不清楚。为此，本项目拟通过联合运用SILAC标记、免疫共沉淀、蛋白质谱和特异位点突变等实验方法，首先鉴定出L2Δ13促食管癌细胞分裂增殖关键相互作用蛋白，然后在分子、细胞和动物实验三个水平上，结合细胞信号通路特异性抑制实验和生物信息学系统分析，深刻揭示L2Δ13促进食管癌细胞分裂增殖分子作用机制。

Our previous researches have observed a significantly abnormal overexpression of a remarkable functional gene of esophageal cancer termed Lysyl Oxidase-Like 2 protein (LOXL2). The function of this very protein was closely related to invasion, migration while was proliferation-independent in esophageal cancer cells. Recently, we discovered a novel splicing isoform of LOXL2 named L2Δ13 for its lack of the thirteenth exon. Through further experimental analysis, L2Δ13 was observed to be detained in cytoplasm and its enzymatic activity was found to reduce extremely comparing to the wild-type as well. Unexpectedly, we uncovered that besides promoting invasion and migration, L2Δ13 also gave the cancer cells stronger abilities to proliferate of which the molecular mechanism still remained a fascinating puzzle. Therefore, in this very project, a series of experimental approaches were designed including stable isotope labeling with amino acids in cell culture (SILAC), immune co-precipitation, protein mass spectrometry analysis, site-directed mutagenesis, etc. to comprehensively identify crucial L2Δ13-interacting proteins involved in cell proliferation promotion. Ultimately, from three aspects namely molecular biology, cytology and animal model, combined with specific inhibition of individual cell signal pathway and systematic bioinformatics analysis, our work profoundly revealed the molecular mechanism of L2Δ13 promoting the cell proliferation in esophageal cancer.