Suppression of Tumorigenicity 5 Ameliorates Tumor Characteristics of Invasive Breast Cancer Cells via ERK/JNK Pathway

Suppression of Tumorigenicity 5 Ameliorates Tumor Characteristics of Invasive Breast Cancer Cells via ERK/JNK Pathway

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BackgroundSuppression of tumorigenicity 5 (ST5) has been considered as a tumor suppressor gene in HeLa tumor cells.However, its role in the progression of breast cancer remains vague.MethodsOnline database analysis was determined by Oncomine and Breast Cancer Gene-Expression Miner v4.4 (bc-GenExMiner v4.

4).Tumor biology behaviors were measured by MTT assay, wound healing crack top frock model, Transwell and Flow cytometry assays.Methylation-specific PCR (MSP) was employed to detect promoter methylation.ResultsLow level of ST5 was observed in breast cancer specimens, particularly in recurrent, invasive breast cancer cases compared to para-carcinoma tissue or non-invasive breast cancer.

The downregulation of ST5 was also proved in MDA-MB-231 and SKBR3 cell lines with a high invasive capability as compared to MCF-7 cell with a low invasive capability.ST5 was negatively associated with pathological stages of breast cancer.ST5-downregulation promoted, while ST5-upregulation inhibited the progression of cell proliferation, cell cycle and migration of MDA-MB-231 cells.Additionally, ST5 knockdown inhibited, whereas ST5 overexpression promoted apoptosis of MDA-MB-231 cells.

However, ST5 modification, either summer beauty ornamental onion upregulation or downregulation, had no significant impact on tumor behaviors of MCF-7 cells.Mechanistically, ST5 protein ablation activated, while ST5-upregulation repressed the activities of phosphorylated ERK1/2 and JNK, and subsequently the expression of c-Myc.PD98059-mediated ERK1/2 inhibition abolished the stimulatory effects of ST5-depletion on ERK1/2/JNK/c-Myc signaling axis, and ST5 depletion-mediated cell over-proliferation and migration.Of note, ST5 reduction in invasive breast cancer cells should implicate in the hypermethylation of ST5 promoter region.

ConclusionOur findings suggest that ST5 potentially acts as a tumor suppressor gene in invasive breast cancer through regulating ERK/JNK signaling pathway and provide a novel insight for breast cancer treatment.