Germline gain‐of‐function MMP11 variant results in an aggressive form of colorectal cancer

Martín-Morales, Lorena; Manzano, Sara; Rodrigo-Faus, María; Vicente-Barrueco, Adrián; Lorca, Víctor; Núñez‐Moreno, Gonzalo; Bragado, Paloma; Porrás, Almudena; Caldés, Trinidad; Garré, Pilar; Gutiérrez-Uzquiza, Álvaro

doi:10.1002/ijc.34289

Cited by 6 publications

(1 citation statement)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our findings showed that MMP11 was overexpressed in many cancers and was associated with a poor prognosis. Previous research has shown that the downregulation of MMP11 expression reduced the growth ability and colony formation ability of cancer cells ( 17 - 19 ). Unlike other MMP members, MMP11 has unique functions and signaling pathways.…”

Section: Discussionmentioning

confidence: 94%

MMP11 as a prognostic biomarker correlated with immune infiltrates in pancreatic adenocarcinoma

Fang,

Xu,

Tao

et al. 2024

J Gastrointest Oncol

View full text Add to dashboard Cite

Background Matrix metalloproteinase 11 ( MMP11 ) plays a vital role in cell proliferation, apoptosis, tumor angiogenesis, migration, and other basic processes. Currently, few studies have examined the value of MMP11 in pancreatic cancer in relation to prognostic risk, diagnostic indicators, and immunotherapy. This study aims to explore the association between MMP11 and the tumor immune microenvironment in pancreatic adenocarcinoma (PAAD). Methods We selected clinical samples and data downloaded from The Cancer Genome Atlas and Genotype-Tissue Expression, in addition, we use other online data for further analysis. Through a comprehensive bioinformatics investigation, we systematically analyzed the clinical significance and expression level of MMP11 in pancreatic cancer. Results MMP11 was overexpressed in many cancers, and a higher expression of MMP11 was associated with a poorer prognosis in pancreatic cancer. Conversely, the hypermethylation of MMP11 was associated with better overall survival. The MMP11 expression network had widespread effects on the prognosis and immune activation of PAAD. The expression of MMP11 was significantly associated with a variety of tumor-infiltrating immune cells. An association was also found between MMP11 expression and chemokines in PAAD. High MMP11 expression might be involved in immune cell migration to the tumor microenvironment. Conclusions MMP11 is a prognostic biomarker for patients in pancreatic cancer and may regulate the tumor immune microenvironment. The potential effects and mechanisms of MMP11 in PAAD require further exploring.

show abstract

Section: Discussionmentioning

confidence: 94%

MMP11 as a prognostic biomarker correlated with immune infiltrates in pancreatic adenocarcinoma

Fang,

Xu,

Tao

et al. 2024

J Gastrointest Oncol

View full text Add to dashboard Cite

show abstract

Matrix metalloproteinase‐11 regulates inverted papilloma epithelial cell migration and invasion

Panara,

Hui,

Keshari

et al. 2024

Int Forum Allergy Rhinol

View full text Add to dashboard Cite

BackgroundInverted papilloma (IP) is a benign tumor characterized by epithelial proliferation, which has the potential for malignant transformation. However, the mechanisms driving this transformation are poorly defined. Matrix metalloproteinase‐11 (MMP‐11), a regulator of the tumor microenvironment that degrades extracellular matrix, is upregulated in IP with dysplasia. Here, we aim to investigate the role of MMP‐11 in IP epithelial migration and invasion.MethodsHuman IP and contralateral normal sinus mucosa (control) samples were obtained. IP‐derived epithelial cultures and normal mucosa‐derived epithelial cultures were grown in air‒liquid interface, followed by immunostaining to assess MMP‐11 expression in IP. Migration and invasion assays were used to evaluate the role of an anti‐MMP‐11 antibody on IP and control epithelial cultures.ResultsIP‐derived cultures demonstrated strong MMP‐11 expression compared to controls. Treatment with anti‐MMP‐11 blocking antibody significantly reduced epithelial migration only in IP‐derived cells compared to non‐treated IP cells, as seen by incomplete wound closure and reduced transepithelial resistance. In addition, inhibition of MMP‐11 reduced IP epithelia's ability to invade through collagen‐coated transwells, suggesting that MMP‐11 plays a role in invasion.ConclusionWe established an in vitro model to study IP‐derived epithelial cells. MMP‐11 is uniquely expressed in IP epithelial cultures compared to control epithelial cultures. Inhibition of MMP‐11 limits IP epithelial migration and invasion to levels similar to that of normal sinus mucosa. MMP‐11 does not appear to have a functional role in normal sinus epithelium, suggesting that MMP‐11 has a role in malignant transformation of IP.

show abstract

Germline gain‐of‐function MMP11 variant results in an aggressive form of colorectal cancer

Martín-Morales

Manzano

Rodrigo-Faus

et al. 2022

Intl Journal of Cancer

View full text Add to dashboard Cite

Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity.

show abstract

Germline gain‐of‐function MMP11 variant results in an aggressive form of colorectal cancer

Cited by 6 publications

References 65 publications

MMP11 as a prognostic biomarker correlated with immune infiltrates in pancreatic adenocarcinoma

MMP11 as a prognostic biomarker correlated with immune infiltrates in pancreatic adenocarcinoma

Matrix metalloproteinase‐11 regulates inverted papilloma epithelial cell migration and invasion

Germline gain‐of‐function MMP11 variant results in an aggressive form of colorectal cancer

Contact Info

Product

Resources

About