GLI1 activation by non-classical pathway integrin αv β3 /ERK1/2 maintains stem cell-like phenotype of multicellular aggregates in gastric cancer peritoneal metastasis

Cell Death & Disease
Hui DongPeiwu Yu

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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Citations

Jul 7, 2020·Frontiers in Cell and Developmental Biology·Diana PáduaPatrícia Mesquita
May 21, 2020·Diagnostic Pathology·Wenbo QiYanhua Xuan
Oct 31, 2021·Journal of Hematology & Oncology·Jiangling XiongDingxiao Zhang

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Methods Mentioned

BETA
lavage
xenograft
PCR
flow cytometry
immunoprecipitation
FACS

Software Mentioned

GraphPad Prism
SPSS

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