Decreased MT1-MMP in gastric cancer suppressed cell migration and invasion via regulating MMPs and EMT

Abstract

Membrane type 1-matrix metalloproteinase (MT1-MMP) has been identified to play a significant role in several types of cancers, but little is known about the significance of MT1-MMP in gastric cancer patients. The purpose of this study is to investigate the involvement of MT1-MMP in tumor progression of gastric cancer. MT1-MMP expression levels were examined in gastric cancer tissues and cells, and normal gastric tissues and cells. The effects and molecular mechanisms of MT1-MMP expression on cell proliferation, migration, and invasion were also explored. In our results, MT1-MMP messenger RNA (mRNA) and protein expression levels were significantly increased in gastric cancer tissue. Moreover, the overexpression of MT1-MMP was positively associated with the status of clinical stage and lymph node metastasis through real-time PCR. Furthermore, knocking down MT1-MMP expression significantly suppressed the cell migration and invasion in vitro and regulated the expression of MMPs and epithelial-mesenchymal transition (EMT)-associated genes. In conclusions, our study demonstrates that MT1-MMP was overexpressed in gastric cancer tissue, and reduced expression of MT1-MMP suppressed cell migration, invasion, and through regulating the expression of MMPs and the process of EMT in gastric cancer.

Down‐regulation of KIF2A inhibits gastric cancer cell invasion via suppressing MT1‐MMP

“…Here we have shown for the first time that KIF2A is a novel upstream molecule of MT1‐MMP in human cancers. Moreover, a study by Wenfeng Li et al has proved that MT1‐MMP is overexpressed in gastric cancer tissue and cell lines, and reduced MT1‐MMP expression suppresses gastric cancer cell migration and invasion but has no influence on cell proliferation: our discovery that the MT1‐MMP level has no obvious influence on gastric cancer cell growth is in accordance with this article.…”

Role of the extracellular matrix in cancer‐associated epithelial to mesenchymal transition phenomenon

“…Moreover, these “pioneer” studies suggest that only breast cancer cells that have acquired the “fibroid phenotype” express the membrane type 1 MMP (MT1‐MMP), which is an activator of MMP‐2 responsible for ECM degradation (Pulyaeva et al, ). Noteworthy, increased activity/expression of MT‐MMP is involved in several cancers, including prostate (Udayakumar et al, ; Haage et al, ), glioblastoma (Munaut et al, ), lung (Zhou et al, ), as well as in gastric cancer tissues (Li et al, ). In continuation, it was revealed that MMPs have a causal role in cancer as stromelysin‐1/MMP‐3, a stromal enzyme up‐regulated in many breast tumors, was found to induce EMT and malignant transformation in vitro through a Rac1/reactive oxygen species axis (Radisky et al, ).…”

“…Moreover, the increased expression of MT1‐MMP was positively correlated with EMT in gastric cancer (Li et al, ). These authors show that an in vitro knockdown of MT1‐MMP decreased migration and invasion as well as reduction of EMT related genes including vimentin, snail, slug, and ZEB1 in gastric cancer cells (Li et al, ).…”

Targeting roles of inflammatory microenvironment in lung cancer and metastasis

“…The invasion and extravasation of cancer cells depend upon proteolytic activities of MMPs through the endothelial barrier and to the distant location for metastasis [87]. MMPs in EMT are considered as phosphatidylinositol 3,4,5-trisphosphate, Akt/PKB protein kinase B, PDK1/2 pyruvate dehydrogenase kinase, isozyme 1,2, mTOR mechanistic target of rapamycin (serine/threonine kinase), IKK inhibitor of nuclear factor kappa-B kinase, IKB nuclear factor of kappa light chain gene enhancer in B-cells inhibitor, CREB cAMP-response element binding protein, GSK3 glycogen synthase kinase 3, BAD BCL2-associated agonist of cell death, CASP9 caspase 9, apoptosis-related cysteine peptidase biomarkers of cancer progression to metastasis [87] and characteristics for tumor cells to invade into surrounding tissues [88]. Primary and metastatic lung cancer cells express MMP-9 constitutively with metastatic potential [89].…”