GLI1 activation by non-classical pathway integrin αv β3 /ERK1/2 maintains stem cell-like phenotype of multicellular aggregates in gastric cancer peritoneal metastasis
Abstract
Peritoneal metastasis is one of the most important causes of postoperative death in patients with gastric cancer, and the exact mechanism remains unclear. The proliferation of multicellular aggregates of exfoliated malignant gastric cells in the abdominal cavity is the focus of current research. However, the mechanism how gastric cancer multicellular aggregates survive remains unclear. In this study, we demonstrated that multicellular aggregates of exfoliated gastric cancer cells in the abdominal cavity expressed a stem cell-Like phenotype. We found that Integrin αvβ3 not only mediated adhesion of gastric cancer multicellular aggregates to form independent functional units, but also maintained their stem cell-like phenotype by the non-classical pathway Integrin αvβ3/ERK1/2/GLI1. In addition, ERK1/2 directly regulates the transcriptional activity of GLI1. GLI1 is a key effector of the Integrin αvβ3 pathway in regulating stem cell-like phenotype in multicellular aggregates. Our data indicates that although there is a crosstalk between the non-classical Integrin αvβ3 pathway and the classical Hedgehog pathway, the activation of GLI1 is almost independent of the Hedgehog pathway in multicellular aggregates of gastric cancer cells. ...Continue Reading
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