Periostin drives extracellular matrix degradation, stemness, and chemoresistance by activating the MAPK/ERK signaling pathway in triple-negative breast cancer cells.
Lipids Health Dis
; 22(1): 153, 2023 Sep 16.
Article
em En
| MEDLINE
| ID: mdl-37716956
ABSTRACT
BACKGROUND:
Adipose tissue, which is mainly composed of adipocytes, is a crucial component of the tumor microenvironment, particularly in breast cancer. Adipocytes surround breast cancer cells and may participate in cellâcell interactions in the breast microenvironment. However, little is currently known about how adipocytes influence the biological behavior of the surrounding breast cancer cells. Hence, this study sought to investigate the role and underlying mechanisms of periostin in triple-negative breast cancer (TNBC) cells cocultured with adipogenic conditioned medium (ACM) and palmitic acid (PA).METHODS:
Human TNBC cell lines (MDAâMBâ231 and SUM159PT) were treated with ACM and PA, then the expression of periostin, matrix metalloproteinases (MMPs) and stemness-related molecules were assessed by Western blotting and RTâqPCR. The cellular viability was assessed using CCKâ8 assay. Plasmid transfection, RNA sequencing, and pathway inhibitor were used to explore the specific mechanisms of periostin.RESULTS:
ACM and PA elevated the expression of both MMPs and stemness-related molecules in TNBCs. MMPs can promote tumor cell infiltration and migration by degrading the extracellular matrix, and stemness expression increases the development of tumor chemoresistance. Additionally, ACM and PA increased periostin expression, while inhibiting periostin disrupted the involvement of ACM and PA in promoting extracellular matrix degradation, stemness, and chemoresistance in TNBCs. Furthermore, this study found that periostin promoted TNBC progression by activating the MAPK/ERK signaling pathway and that inhibition of MAPK/ERK signaling reduced the phenotype caused by periostin upregulation in TNBCs treated with ACM or PA. Finally, the present results showed that the high expression of POSTN, which encodes periostin, was substantially related to worse survival in TNBC patients.CONCLUSIONS:
The results of the study elucidated for the first time how periostin is the key protein secreted in TNBCs in response to the adipocyte-regulated tumor microenvironment, while periostin-neutralizing antibodies may serve as potential therapeutic agents in relation to TNBC progression.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias de Mama Triplo Negativas
Limite:
Humans
Idioma:
En
Revista:
Lipids Health Dis
Assunto da revista:
BIOQUIMICA
/
METABOLISMO
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China