Rare Diseases Symptoms Automatic Extraction

Endosomal WASH and exocyst complexes control exocytosis of MT1-MMP at invadopodia.

[wiskott-aldrich syndrome]

Remodeling of the extracellular matrix by carcinoma cells during metastatic dissemination requires formation of actin-based protrusions of the plasma membrane called invadopodia, where the trans-membrane type 1 matrix metalloproteinase (MT1-MMP) accumulates. Here, we describe an interaction between the exocyst complex and the endosomal Arp2/3 activator Wiskott-Aldrich syndrome protein and Scar homolog (WASH) on MT1-MMP–containing late endosomes in invasive breast carcinoma cells. We found that WASH and exocyst are required for matrix degradation by an exocytic mechanism that involves tubular connections between MT1-MMP–positive late endosomes and the plasma membrane in contact with the matrix. This ensures focal delivery of MT1-MMP and supports pericellular matrix degradation and tumor cell invasion into different pathologically relevant matrix environments. Our data suggest a general mechanism used by tumor cells to breach the basement membrane and for invasive migration through fibrous collagen-enriched tissues surrounding the tumor.

Diseases presenting "tumor cells" symptom

  • alpha-thalassemia
  • carcinoma of the gallbladder
  • cholangiocarcinoma
  • cushing syndrome
  • dedifferentiated liposarcoma
  • dentin dysplasia
  • esophageal adenocarcinoma
  • esophageal carcinoma
  • esophageal squamous cell carcinoma
  • hodgkin lymphoma, classical
  • junctional epidermolysis bullosa
  • kindler syndrome
  • liposarcoma
  • lymphangioleiomyomatosis
  • pleomorphic liposarcoma
  • primary effusion lymphoma
  • severe combined immunodeficiency
  • triple a syndrome
  • von hippel-lindau disease
  • waldenström macroglobulinemia
  • well-differentiated liposarcoma
  • werner syndrome
  • wiskott-aldrich syndrome

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