biostudies-literatureUnknown9(7)Liu W<h4>Background</h4>Triple-negative breast cancer (TNBC) is a subtype of invasive breast cancer that tests negative for PR, ER and excess HER2 protein. TNBC has a greater progression potential with poorer prognosis, compared with other types of breast cancer. Endothelial cell-specific molecule 1 (ESM1), also known as endocan, is overexpressed in various cancers including breast cancer and may play an important role in cancer progression.<h4>Methods</h4>The online resource of The Cancer Genome Atlas (TCGA) was used for analyzing the expression alteration of <i>ESM1</i> in breast cancer patient tissues. We examined the changes of various malignant behaviors of TNBC cell and <i>in vivo</i> tumor growth after inhibiting or overexpressing ESM1 in two human TNBC cell lines, MDA-MB-468 and MDA-MB-231. When ESM1 was knocked down or overexpressed in TNBC cell, AKT and p65 phosphorylation and Cyclin D1 expression were analyzed by western blotting. The ESM1-overexpressing TNBC cell was treated with MK-2206 and BAY-117082 at various concentrations.<h4>Results</h4>Our analyses show that <i>ESM1</i> is overexpressed in TNBC cell lines as well as patient tissues, which is correlated to poor prognosis. Our results demonstrate that ESM1 knockdown decreases while overexpression of ESM1 increases <i>in vitro</i> proliferation, migration and invasion of TNBC cell and knockdown of ESM1 inhibits <i>in vivo</i> TNBC tumor growth. Our mechanistic study further discloses that ESM1 promotes the proliferation of TNBC cell through activating an Akt-dependent NF-κB/Cyclin D1 pathway.<h4>Conclusions</h4>Our results demonstrate that ESM1 knockdown decreases while overexpression of ESM1 increases <i>in vitro</i> migration, proliferation and invasion of TNBC cell and knockdown of ESM1 inhibits <i>in vivo</i> tumor growth of TNBC in the xenograft mouse model. Our mechanistic study further discloses that ESM1 promotes the proliferation of TNBC cell through activating the Akt-dependent NF-κB/CyclinD1 pathway. Our findings expand the knowledge about the molecular mechanisms underlying TNBC progression and provide rationale for using ESM1 as a therapeutic target or prognostic marker for TNBC.Annals of translational medicine533https://www.ebi.ac.uk/biostudies/studies/S-EPMC8105853biostudies-literatureESM1 promotes triple-negative breast cancer cell proliferation through activating AKT/NF-κB/Cyclin D1 pathway.PMC8105853Guo MYang YDong ZSun FZhang MHe BMa FLiu WfalseESM1 promotes triple-negative breast cancer cell proliferation through activating AKT/NF-κB/Cyclin D1 pathway.<h4>Background</h4>Triple-negative breast cancer (TNBC) is a subtype of invasive breast cancer that tests negative for PR, ER and excess HER2 protein. TNBC has a greater progression potential with poorer prognosis, compared with other types of breast cancer. Endothelial cell-specific molecule 1 (ESM1), also known as endocan, is overexpressed in various cancers including breast cancer and may play an important role in cancer progression.<h4>Methods</h4>The online resource of The Cancer Genome Atlas (TCGA) was used for analyzing the expression alteration of <i>ESM1</i> in breast cancer patient tissues. We examined the changes of various malignant behaviors of TNBC cell and <i>in vivo</i> tumor growth after inhibiting or overexpressing ESM1 in two human TNBC cell lines, MDA-MB-468 and MDA-MB-231. When ESM1 was knocked down or overexpressed in TNBC cell, AKT and p65 phosphorylation and Cyclin D1 expression were analyzed by western blotting. The ESM1-overexpressing TNBC cell was treated with MK-2206 and BAY-117082 at various concentrations.<h4>Results</h4>Our analyses show that <i>ESM1</i> is overexpressed in TNBC cell lines as well as patient tissues, which is correlated to poor prognosis. Our results demonstrate that ESM1 knockdown decreases while overexpression of ESM1 increases <i>in vitro</i> proliferation, migration and invasion of TNBC cell and knockdown of ESM1 inhibits <i>in vivo</i> TNBC tumor growth. Our mechanistic study further discloses that ESM1 promotes the proliferation of TNBC cell through activating an Akt-dependent NF-κB/Cyclin D1 pathway.<h4>Conclusions</h4>Our results demonstrate that ESM1 knockdown decreases while overexpression of ESM1 increases <i>in vitro</i> migration, proliferation and invasion of TNBC cell and knockdown of ESM1 inhibits <i>in vivo</i> tumor growth of TNBC in the xenograft mouse model. Our mechanistic study further discloses that ESM1 promotes the proliferation of TNBC cell through activating the Akt-dependent NF-κB/CyclinD1 pathway. Our findings expand the knowledge about the molecular mechanisms underlying TNBC progression and provide rationale for using ESM1 as a therapeutic target or prognostic marker for TNBC.2021-01-01T00:00:00Z2021 Apr2025-05-29T16:36:10.421Z2025-05-29T16:36:10.421ZS-EPMC81058533398723110.21037/atm-20-7005