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IL-37bΔ1-45 suppresses the migration and invasion of endometrial cancer cells by targeting the Rac1/NF-κB/MMP2 signal pathway

Abstract

Endometrial carcinoma is one of the most common malignancies in the female reproductive system. Interleukin-37 (IL-37) is a newly discovered anti-inflammatory factor belonging to the IL-1 family. IL-37 has five different isoforms, and IL-37b is the most biologically functional subtype. In recent years, the protective roles of IL-37 in different cancers, including lung and liver cancers, have been successively reported. IL-37 also plays an important role in some gynecological diseases such as endometriosis, adenomyosis, and cervical cancer. However, the role and mechanism of IL-37b, especially the mature form of IL-37b, in endometrial carcinoma have not been elucidated. The present study demonstrated that IL-37 protein was downregulated in endometrial carcinoma cells compared with the control endometrium. IL-37b did not affect the proliferation and colony-forming ability of endometrial cancer cells. A mature form of IL-37b (IL-37bΔ1-45) effectively suppressed the migration and invasion of endometrial cancer cells by decreasing the expression of matrix metalloproteinase 2 (MMP2) via Rac1/NF-κB signal pathway. However, it did not affect epithelial–mesenchymal transition (EMT) or filamentous actin (F-actin) depolymerization of endometrial cancer cells. IL-37bΔ1-45 attenuated tumor metastasis in a peritoneal metastatic xenograft model of endometrial cancer. To sum up, these results suggested IL-37b could be involved in the pathogenesis of endometrial carcinoma and provide a novel target for the diagnosis and treatment of endometrial carcinoma.

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Fig. 1: The expression of IL-37 protein was downregulated in endometrioid adenocarcinoma cells detected by IHC.
Fig. 2: IL-37b overexpression or knockdown increased or decreased the expression of IL-37 at mRNA and protein levels.
Fig. 3: IL-37b did not affect the proliferation and colony formation ability of endometrial cancer cells.
Fig. 4: IL-37b suppressed the migration and invasion ability of endometrial cancer cells.
Fig. 5: IL-37b decreased the expression of MMP2 by Rac1/NF-κB signal pathway in endometrial cancer cells.
Fig. 6: IL-37b suppressed the migration and invasion ability of endometrial cancer cells by the Rac1/NF-κB/MMP2 signal pathway.
Fig. 7: IL-37b attenuated tumor metastasis in the peritoneal metastatic xenograft model of endometrial cancer.
Fig. 8: IL-37b inhibits tumor metastasis in vivo by the degradation of the basement membrane.

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Correspondence to Xiaoyan Wang.

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Wang, X., Wei, Z., Tang, Z. et al. IL-37bΔ1-45 suppresses the migration and invasion of endometrial cancer cells by targeting the Rac1/NF-κB/MMP2 signal pathway. Lab Invest (2021). https://doi.org/10.1038/s41374-021-00544-2

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