TIPE1 suppresses the invasion and migration of breast cancer cells and inhibits epithelial-to-mesenchymal transition primarily via the ERK signaling pathway

Abstract

Tumor necrosis factor α-induced protein 8-like-1 (TIPE1) functions as an activator or a repressor in a tumor cell type-specific manner. However, the role of TIPE1 in breast cancer, especially regarding metastasis, is unknown. In this study, we aimed to investigate the TIPE1 expression in breast cancer tissues, the biological functions, and the underlying mechanisms of TIPE1 regarding the metastatic properties of breast cancer cells. The results of immunohistochemical staining and western blot analysis indicated that TIPE1 expression was associated with tumor size and lymph node metastasis, and the expression of TIPE1 was downregulated in the tissues of patients with lymph node metastasis. Transwell and wound healing assay results showed that TIPE1 inhibited the invasive and migratory capacities of breast cancer cells. Moreover, the epithelial-mesenchymal transition (EMT) was suppressed in TIPE1-overexpressing cells, as demonstrated by western blot analysis. In addition, western blot analysis also showed that TIPE1 reduced the expression levels of MMP2 and MMP9 and decreased the phosphorylation level of ERK. These results suggested that TIPE1 might suppress the invasion and migration of breast cancer cells and inhibit EMT primarily via the ERK signaling pathway. Our findings revealed the anti-tumor metastasis role of TIPE1 in breast cancer and TIPE1 might be a new candidate prognostic indicator and a potential molecular target for the treatment of breast cancer.

Integrative Bioinformatics Analysis Reveals Potential Target Genes and TNFα Signaling Inhibition by Brazilin in Metastatic Breast Cancer Cells

“…Activation of NFkB by TNFα promotes breast cancer by promoting (Kawabata et al, 2017). TNFα signaling also activates the ERK/JNK/p38 pathway leading to migration and invasion in colon cancer cells (Zhao and Zhang, 2018), and breast cancer cells (Qiu et al, 2019). Another study demonstrated that TNFα activates mesenchymal stromal cells that leads to metastasis in breast cancer through the recruitment of CXCR2+ neutrophils (Yu et al, 2017).…”

TIPE1‐mediated autophagy suppression promotes nasopharyngeal carcinoma cell proliferation via the AMPK/mTOR signalling pathway

“…22 TIPE1 is also present in many cancer cells of epithelial origin, including breast, cervical, bladder and gastric cancer cells. 11,13,[22][23][24][25] To date, a great deal of evidence has shown that TIPE1 plays crucial roles in the carcinogenesis of many cancers, including hepatocellular carcinoma, gastric cancer, lung cancer, osteosarcoma, cervical Autophagy has been shown to be intimately related with cancer. [27][28][29] In this study, the decreased density of characteristic autophagosomes and the decreased expression of LC3B in tumour tissue sections provided strong evidence that autophagy was inhibited after TIPE1 was overexpressed.…”

“…22 TIPE1 is also present in many cancer cells of epithelial origin, including breast, cervical, bladder and gastric cancer cells. 11,13,[22][23][24][25] To date, a great deal of evidence has shown that TIPE1 plays crucial roles in the carcinogenesis of many cancers, including hepatocellular carcinoma, gastric cancer, lung cancer, osteosarcoma, cervical cancer, colon cancer and breast cancer. TIPE1 can induce apoptosis in RAW264.7 and hepatocellular carcinoma cells by increasing the levels of Bcl-2 family proteins or down-regulating the Rac1 pathway.…”

<p>Regulatory Roles of Tumor Necrosis Factor-α-Induced Protein 8 Like-Protein 2 in Inflammation, Immunity and Cancers: A Review</p>

“…23 Additionally, in breast cancer cells, TIPE1 suppressed the proliferation, invasion, metastasis, and EMT via downregulating the phosphorylation of extracellular signal-regulated protein kinase (ERK). 24 In osteosarcoma, TIPE1 was found to suppress the activity of monocyte chemotactic protein-1 (MCP-1) to reduce macrophage infiltration, thus inhibiting the proliferation of osteosarcoma cells [38]. 25 In hematological diseases, TIPE1 was observed to promote cell apoptosis and inhibit tumor growth in RAW264.7 cells by upregulating pro-apoptotic members of the B cell lymphoma/leukemia-2 (Bcl-2) family.…”