Cell adhesion molecule L1-like protein regulates neuregulin-ErbB receptor signaling in glioma cells

Abstract

Objective: It was previously demonstrated that the cytokine neuregulin 1 (NRG1) can promote the proliferation of glioma cells by modulating cell adhesion molecule L1-like (CHL1) protein expression in glioma development. However, the role of CHL1 in NRG signaling modulation remains to be elucidated. In the present study, the effects of CHL1 on NRG signaling in three glioma/glioblastoma cell lines were explored mainly by using small interfering RNAs (siRNAs) targeting CHL1.

Methods: SHG44 and U251 glioma, and U-87 MG glioblastoma cells were treated with siRNA targeting CHL1 for 48 h. Then, the protein expression of NRG1-4, and their cognate receptors pErbB2-4 was evaluated by western blot in these cell lines. Immunofluorescence staining was used to evaluate the effect of CHL1 on pErbB2 and pErbB4.

Results: siRNA targeting CHL1 significantly and differentially downregulated the expression of the main NRG subtypes, including NRG1, 2, 3 and 4. Downregulation of CHL1 expression also reduced the level of phosphorylated (p) activated NRG receptors p-ErbB2, 3 and 4.

Conclusions: Overall, these data indicated that CHL1 may contribute to glioma malignancy by upregulating NRG signaling in glioma/glioblastoma cells.