Upregulated MMP28 in Hepatocellular Carcinoma Promotes Metastasis via Notch3 Signaling and Predicts Unfavorable Prognosis

Zhou, Jiangfan; Zheng, Xiangqun; Feng, Mei; Mo, Zhichao; Shan, Yunfeng; Wang, Yilin; Jin, Jing

doi:10.7150/ijbs.31335

Cited by 16 publications

(22 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MMP28 is also overexpressed in gastric cancer and is related to lymph node metastasis, tumor invasion, and poor OS [50]. The role of MMP28 in promoting metastasis via Notch3 signaling was also presented in hepatocellular carcinoma [51].…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a metastasis-related Gene Signature for predicting the Overall Survival in patients with Pancreatic Ductal Adenocarcinoma

Wu¹,

Li²,

Li³

et al. 2020

J. Cancer

View full text Add to dashboard Cite

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal, aggressive cancer characterized by invasiveness and metastasis. In this study, we aimed to propose a gene prediction model based on metastasis-related genes (MTGs) to more accurately predict PDAC prognosis. Methods: Differentially expressed MTGs (DE-MTGs) were identified via integrated analysis of gene expression omnibus (GEO) datasets and Human Cancer Metastasis Database (HCMDB). Overall survival (OS) related DE-MTGs were then identified and a prognostic gene signature was established using Lasso-Cox regression with TCGA-PAAD datasets. Tumor immunity was analyzed using ESTIMATE and CIBERSORT algorithms. Finally, a nomogram predicting 1-year, 2-year, and 3-year OS of PDAC patients was established based on the prognostic gene signature and relevant clinical parameters using a stepwise Cox regression model. Results: A total of 36 DE-MTGs related to OS were identified in PDAC. Consequently, an MTG-based gene signature comprising of RACGAP1, RARRES3, TPX2, MMP28, GPR87, KIF14, and TSPAN7 was established to predict the OS of PDAC. The MTG-based gene signature was able to distinguish high-risk patients with significantly poorer prognosis and accurately predict OS of PDAC in both the training and external validation datasets. Cox regression analysis indicated that the MTG-based gene signature was an independent prognostic factor in PDAC. The gene set enrichment analysis (GSEA) showed that molecular alterations in the high-risk group were associated with multiple oncological pathways. Moreover, analysis of tumor immunity revealed significantly higher levels of follicular helper T cells and M0 macrophage infiltration, and lower levels of infiltrating naïve B cells, CD8 T cells, monocytes, and resting dendritic cells in the high-risk group. Immune cell infiltration levels were significantly associated with the expression of the seven DE-MTGs. Finally, a nomogram was established by incorporating the prognostic gene signature and clinical parameters, which was superior to the AJCC staging system in predicting the OS of PDAC patients. Conclusions: The DE-MTGs we identified were closely associated with the progress and prognosis of PDAC and are potential therapeutic targets. The MTG-based gene signature and nomogram may serve to improve the individualized prediction of survival, assisting in clinical decision-making.

show abstract

Section: Discussionmentioning

confidence: 99%

Development and validation of a metastasis-related Gene Signature for predicting the Overall Survival in patients with Pancreatic Ductal Adenocarcinoma

Wu¹,

Li²,

Li³

et al. 2020

J. Cancer

View full text Add to dashboard Cite

show abstract

“…MMP-28 promotes and maintains EMT through activation of TGF- β signaling and upregulating Snail transcription factor [72]. Elevated levels of MMP-28 in HCC are correlated with a poor prognosis, due to higher TNM stage and increased rates of portal vein invasion and metastasis, the latter apparently depending on Notch3 signals [73].…”

Section: Mmps With a Demonstrated Role In The Emt Of Invasive Hccmentioning

confidence: 99%

The Role of Matrix Metalloproteinases in the Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma

Scheau

Bădărău

Costache

et al. 2019

Analytical Cellular Pathology

272

219

View full text Add to dashboard Cite

The epithelial-mesenchymal transition (EMT) is a transformation process mandatory for the local and distant progression of many malignant tumors, including hepatocellular carcinoma (HCC). Matrix metalloproteinases (MMPs) play significant roles in cellular regeneration, programmed death, angiogenesis, and many other essential tissular functions, involved in the normal development and also in pathological processes, such as the EMT. This paper reviews the roles of MMPs in the EMT involved in HCC invasion, as well as the ancillary roles that MMP cross-activation and tissue inhibitors play in modulating this process. While gelatinases MMP-2 and MMP-9 are the MMPs commonly cited in the EMT of HCC, MMPs belonging to other classes have been proven to be involved in this process, favoring not only invasion and metastasis (MMP-1, MMP-3, MMP-7, MMP-10, MMP-11, MMP-13, MMP-14, MMP-16, MMP-26, and MMP-28) but also angiogenesis (MMP-8 and MMP-10). There is also data suggesting that other MMPs with a suspected or demonstrated role in the EMT of other cancers may also have some degree of involvement in HCC. The auto- and cross-activation of MMPs may complicate this issue, as pinpointing the extent of implication of each MMP may be extremely difficult. The homeostasis between MMPs and their tissue inhibitors is essential in preventing tumor progression, and the disturbance of this stability is another entailed factor in the EMT of HCC, which is addressed herein.

show abstract

“…In cancer, MMP28 is detected in numerous tumour types. MMP28 promotes cell proliferation in oral squamous cell carcinoma 43 while in gastric cancer 17 and hepatocellular carcinoma 44 (HCC) there is a clear association with poor prognosis. In HCC cell lines, MMP28 overexpression promotes EMT via activation of zeb1 and zeb2 downstream of the Notch pathway 44 .…”

Section: Discussionmentioning

confidence: 99%

Paracrine regulation of neural crest EMT by placodal MMP28

Gouignard

Bibonne

Mata

et al. 2020

Preprint

View full text Add to dashboard Cite

Epithelial-Mesenchymal Transition (EMT) is an early event in cell dissemination from epithelial tissues. EMT endows cells with migratory, and sometimes invasive, capabilities and is thus a key process in embryo morphogenesis and cancer progression. So far, Matrix Metalloproteinases (MMPs) have not been considered as key players in EMT but rather studied for their role in matrix remodelling in later events such as cell migration per se. Here we used Xenopus neural crest cells to assess the role of MMP28 in EMT and migration in vivo. We provide strong evidence indicating that MMP28 produced by neighbouring placode cells is imported in the nucleus of neural crest cells for EMT and migration to occur.

show abstract

Upregulated MMP28 in Hepatocellular Carcinoma Promotes Metastasis via Notch3 Signaling and Predicts Unfavorable Prognosis

Cited by 16 publications

References 49 publications

Development and validation of a metastasis-related Gene Signature for predicting the Overall Survival in patients with Pancreatic Ductal Adenocarcinoma

Development and validation of a metastasis-related Gene Signature for predicting the Overall Survival in patients with Pancreatic Ductal Adenocarcinoma

The Role of Matrix Metalloproteinases in the Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma

Paracrine regulation of neural crest EMT by placodal MMP28

Contact Info

Product

Resources

About