AI Article Synopsis
- Metastasis is a leading cause of cancer deaths and is heavily influenced by the protease MT1-MMP, which plays a key role in local invasion and spreading of cancer cells.
- The transport of MT1-MMP from the endoplasmic reticulum to invadopodia is complex and involves the diversion of a protein called Bet1, which typically helps in transporting other proteins to the Golgi apparatus.
- The study finds that MT1-MMP's interaction with Bet1 and other proteins facilitates its movement to the cell surface, enhancing its role in cancer cell invasiveness.
Article Abstract
Metastasis is a major cause of cancer-related death. Membrane type 1-matrix metalloproteinase (MT1-MMP) is a critical protease for local invasion and metastasis. MT1-MMP is synthesized in the endoplasmic reticulum (ER) and transported in vesicles to invadopodia, specialized subdomains of the plasma membrane, through secretory and endocytic recycling pathways. The molecular mechanism underlying intracellular transport of MT1-MMP has been extensively studied, but is not fully understood. We show that MT1-MMP diverts the SNARE Bet1 from its function in ER-Golgi transport, to promote MT1-MMP trafficking to the cell surface, likely to invadopodia. In invasive cells, Bet1 is localized in MT1-MMP-positive endosomes in addition to the Golgi apparatus, and forms a novel SNARE complex with syntaxin 4 and endosomal SNAREs. MT1-MMP may also use Bet1 for its export from raft-like structures in the ER. Our results suggest the recruitment of Bet1 at an early stage after MT1-MMP expression promotes the exit of MT1-MMP from the ER and its efficient transport to invadopodia.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781441 | PMC |
| http://dx.doi.org/10.1083/jcb.201808149 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A Versatile Skin-Derived Extracellular Matrix Hydrogel-Based Platform to Investigate the Function of a Mechanically Isolated Adipose Tissue Stromal Vascular Fraction.
Biomolecules
November 2024
Department of Pathology and Medical Biology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
To accelerate cutaneous wound healing and prevent scarring, regenerative approaches such as injecting a mechanically derived tissue stromal vascular fraction (tSVF) are currently under clinical and laboratory investigations. The aim of our study was to investigate a platform to assess the interaction between skin-derived extracellular matrix (ECM) hydrogels and tSVF and their effects on their microenvironment in the first ten days of culture. A tSVF mixed with ECM hydrogel was cultured for ten days.
View Article and Find Full Text PDFTFEB triggers a matrix degradation and invasion program in triple-negative breast cancer cells upon mTORC1 repression.
Dev Cell
December 2024
Institut Curie, CNRS UMR 144, PSL University, 75005 Paris, France. Electronic address:
The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is frequently hyperactivated in triple-negative breast cancers (TNBCs) associated with poor prognosis and is a therapeutic target in breast cancer management. Here, we describe the effects of repression of mTOR-containing complex 1 (mTORC1) through knockdown of several key mTORC1 components or with mTOR inhibitors used in cancer therapy. mTORC1 repression results in an ∼10-fold increase in extracellular matrix proteolytic degradation.
View Article and Find Full Text PDFGradual expression of MMP9 and MT1-MMP at the tumor-stroma interface in head and neck squamous cell carcinoma.
Histol Histopathol
December 2024
Laboratory of Experimental Medicine, Centre Hospitalier Universitaire de Charleroi-Chimay, Université Libre de Bruxelles, Montigny-le-Tilleul, Belgium.
Due to the late-stage diagnosis of head and neck squamous cell carcinoma (HNSCC), treatment remains a significant clinical challenge. The metalloproteinases MMP-9 and MT1-MMP play a pivotal role in extracellular matrix remodeling, thereby facilitating tumor growth and metastasis. Tumor progression requires the degradation of the basement membrane.
View Article and Find Full Text PDFDura immunity configures leptomeningeal metastasis immunosuppression for cerebrospinal fluid barrier invasion.
Nat Cancer
December 2024
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
The cerebrospinal fluid (CSF) border accommodates diverse immune cells that permit peripheral cell immunosurveillance. However, the intricate interactions between CSF immune cells and infiltrating cancer cells remain poorly understood. Here we use fate mapping, longitudinal time-lapse imaging and multiomics technologies to investigate the precise origin, cellular crosstalk and molecular landscape of macrophages that contribute to leptomeningeal metastasis (LM) progression.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!