Role And Molecular Mechanism Of ESM1 In Triple-negative Breast Cancer Cell Proliferation And Invasion

Global cancer morbidity and mortality are increasing rapidly.Breast cancer is the most common cancer among women worldwide and the leading cause of cancer-related deaths among women.Triple-negative breast cancer refers to the unique type of breast cancer that is negative for ER,PR,and Her2,and accounts for10%-20% of all breast cancers.Compared with other subtypes of breast cancer,triple-negative breast cancer has the characteristics of young incidence,high malignancy,easy recurrence and metastasis,and low survival rate.In addition to the lack of endocrine therapy and targeted therapy,triple-negative breast cancer has become one of the biggest challenges of the current breast cancer treatment.Endothelial cell-specific molecule 1(ESM1)is a sulfated skin proteoglycan that can circulate freely in the blood.Previous studies have found that ESM1 is significantly overexpressed in lung cancer,uterine cancer,kidney cancer,liver cancer,glioblastoma and breast cancer.There is evidence that ESM1 is directly involved in tumor progression and has a significant impact on cancer cell proliferation and migration in Nasopharyngeal cancer,head and neck cancer and liver cancer.It is recently reported that ESM1 can be used as a prognostic marker for triple-negative breast cancer.Therefore,it is of great significance to study the role and mechanism of ESM1 in triple-negative breast cancer.This study aims to explore the role of ESM1 in the cancer cell proliferation,migration and invasion of triple-negative breast cancer.We applied human triple-negative breast cancer cell lines MDA-MB-231,MDA-MB-468 for knockdown and overexpression of ESM1.We used transwell migration and invasion analysis,cck8 cell viability assay,and colony formation assay to examine TNBC cell proliferation,migration and invasion ability in vitro,and adopted nude mice tumor-bearing experiment to inspect the effect of ESM1 knockdown on tumor proliferation in vivo.Our results are summarized as follows: 1.The transwell cell migration assay showed that compared with the control,the TNBC migration ability of the ESM1 knockdown group was significantly reduced;the TNBC cell migration ability of the ESM1 overexpression group was significantly higher than that of the control group 2.Transwell cell invasion experiment showed that compared with the control,the TNBC invasion ability of the ESM1 knockdown group significantly decreased;the TNBC cell invasion ability of the ESM1 overexpression group was significantly higher than that of the control group 3.The results of CCK-8 assay showed that the absorbance value of the ESM1 knockdown group was significantly lower than that of the control group at each time point,which indicates that the proliferative capacity of the TNBC cells was reduced;the absorbance value of the ESM1 overexpression group was significantly higher than the control group,indicating a increased TNBC proliferative capacity.4.The results of colony formation experiments showed that compared with the control group,the number of cell colony formation in the ESM1 knockdown group was significantly reduced;the number of cell clone formation in the ESM1 overexpression group was significantly increased compared with the control group 5.Mouse tumor-bearing experiment showed that compared with the control group,ESM1 knockdown significantly inhibited tumor growth.In summary,our study demonstrates that ESM1 can promote the proliferation,migration and invasion of triple-negative breast cancer cells and the in vivo tumor growth,thereby playing an important role in tumor progression.The underlying mechanism needs to be further studied.Our study deepens the understanding of the molecular mechanism of triple-negative breast cancer progression and provides a theoretical basis for exploring new prognostic markers and novel therapeutic targets.