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 (MT 1 -MMP ) accumulates . Here , we describe an interaction between the exocyst complex and the endosomal Arp 2 /3 activator Wiskott-Aldrich syndrome protein and Scar homolog (WASH ) on MT 1 -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 MT 1 -MMP–positive late endosomes and the plasma membrane in contact with the matrix . This ensures focal delivery of MT 1 -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
Validation

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

You can validate or delete this automatically detected symptom