Crosstalk between MMP-13, CD44, and TWIST1 and its role in regulation of EMT in patients with esophageal squamous cell carcinoma.
Aged
Epithelial-Mesenchymal Transition
Esophageal Neoplasms
/ genetics
Esophageal Squamous Cell Carcinoma
/ genetics
Female
Humans
Hyaluronan Receptors
/ genetics
Male
Matrix Metalloproteinase 13
/ genetics
Middle Aged
Neoplasm Proteins
/ genetics
Nuclear Proteins
/ genetics
Twist-Related Protein 1
/ genetics
EMT
ESCC
Invasion
Matrix metalloproteinase
Journal
Molecular and cellular biochemistry
ISSN: 1573-4919
Titre abrégé: Mol Cell Biochem
Pays: Netherlands
ID NLM: 0364456
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
received:
16
07
2020
accepted:
29
01
2021
pubmed:
20
2
2021
medline:
29
7
2021
entrez:
19
2
2021
Statut:
ppublish
Résumé
Matrix metalloproteinases (MMPs) play key roles in epithelial-mesenchymal transition (EMT) for the development of cancer cell invasion and metastasis. MMP-13 is an extracellular matrix (ECM)-degrading enzyme that plays crucial roles in angiogenesis, cell cycle regulation, niche maintenance, and transforming squamous epithelial cells in various tissues. CD44, a transmembrane glycoprotein expressed on esophageal tumor cells, is required for EMT induction and invasion in esophageal squamous cell carcinoma (ESCC). The transcription factor TWIST1, as EMT and stemness marker, regulates MMPs expression and is identified as the downstream target of CD44. In this study, we aimed to investigate the probable interplay between the expression of key genes contributing to ESCC development, including MMP-13, TWIST1, and CD44 with clinical features for introducing novel diagnostic and therapeutic targets in the disease. The gene expression profiling of MMP-13, TWIST1, and CD44 was performed using quantitative real-time PCR in tumor tissues from 50 ESCC patients compared to corresponding margin non-tumoral tissues. Significant overexpression of MMP-13, CD44S, CD44V3, CD44V6, and TWIST1 were observed in 74%, 36%, 44%, 44%, and 52% of ESCC tumor samples, respectively. Overexpression of MMP-13 was associated with stage of tumor progression, metastasis, and tumor location (P < 0.05). There was a significant correlation between TWIST1 overexpression and grade (P < 0.05). Furthermore, overexpression of CD44 variants was associated with stage of tumor progression, grade, tumor invasion, and location (P < 0.05). The results indicated the significant correlation between concomitant expression of MMP-13/TWIST1, TWIST1/CD44, and CD44/MMP-13 with each other in a variety of clinicopathological traits, including depth of tumor invasion, tumor location, stage of tumor, and lymph node involvement in ESCC tissue samples (P < 0.05). Collectively, our results indicate that the TWIST1-CD44-MMP-13 axis is involved in tumor aggressiveness, proposing these genes as regulators of EMT, diagnostic markers, and therapeutic targets in ESCC.
Identifiants
pubmed: 33604811
doi: 10.1007/s11010-021-04089-2
pii: 10.1007/s11010-021-04089-2
doi:
Substances chimiques
CD44 protein, human
0
Hyaluronan Receptors
0
Neoplasm Proteins
0
Nuclear Proteins
0
TWIST1 protein, human
0
Twist-Related Protein 1
0
MMP13 protein, human
EC 3.4.24.-
Matrix Metalloproteinase 13
EC 3.4.24.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2465-2478Subventions
Organisme : Mashhad University of Medical Sciences
ID : 941435
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