肿瘤多细胞团簇（MCAs）是肿瘤转移中的独立结构单元，生物学功能备受关注。腹腔脱落胃癌细胞通常以MCAs形式存在，是胃癌腹腔转移真正“种子”细胞，前期研究发现胃癌腹腔转移MCAs主要以Integrinαvβ3介导粘附聚集而成，具有肿瘤干样细胞特性，但干性维持机制不清。本项目基于前期研究结果，推测胃癌腹腔转移MCAs中Integrinαvβ3/MAPK与Hedgehog-GLI1通路发生crosstalk，Integrinαvβ3/MAPK以非经典途径活化GLI1维持MCAs肿瘤干细胞特性。本课题拟以胃癌MCAs为研究对象，应用分子生物学、体外激酶活性测定、质谱分析等方法证实Integrinαvβ3/MAPK通路磷酸化GLI1丝/苏氨酸，活化GLI1，启动干细胞核转录因子表达，维持MCAs干样特性。从而深入揭示胃癌腹腔转移MCAs干性调节分子机制，为胃癌腹腔转移防治提供新的理论依据。

Tumor multicellular aggregates (MCAs) is an independent structure unit，and is widespread concerned about its biological function. The exfoliated gastric cancer cells are consisted of mainly MCAs, which are the actual “seed” cells during the process of peritoneal metastasis for gastric cancer. In previous study we found MCAs are aggregated together by Integrin alpha v beta 3, and MCAs are acquired tumor stem-like characteristics, however the underlying mechanism of sustaining stemness for MCAs is still unclear. Based on recent literature and the results of previous studies, we postulate that crosstalk occurred between Integrinαvβ3/MAPK and Hedgehog pathways in MCAs, GLI1 is activated and the stemness is contained by Integrinαvβ3/MAPK pathway in a noncanonical way. This project intends to revolve around abdominal gastric MCAs, confirms Integrinαvβ3/MAPK phosphorylation of GLI1 by direct serine/threonine, activate GLI1, starting downstream associated nuclear transcription factors expression, thereby maintaining the MCAs cancer stem cells by using molecular biology, in vitro kinase activity assays, and mass spectrometry analysis. In vivo experiment further verifies these results. Thereby reveal the mechanism of abdominal gastric MCAs stemness maintenance, thus offer a novel theoretical basis for the prevention and treatment of peritoneal metastasis.