Chavrier

Membrane and Cytoskeleton Dynamics

Philippe Chavrier
Scientific keywords: actin cytoskeleton, breast cancer, matrix metalloproteinases, membrane traffic, tumor cell invasion
Technics Used in the Lab: Real time imaging, immunofluorescence, molecular biology, 3D invasion assay, xenograft

One major route of invasion requires cancer cells to proteolytically cleave extracellular matrix components via a mechanism based upon the formation of invadopodia. These specialized structures of invasive cells correspond to sites of actin filament assembly and accumulation of MT1-MMP, a trans-membrane metalloproteinase crucial for matrix degradation and invasion. How actin assembly, signaling and membrane trafficking are integrated to produce the matrix degrading machinery of invasive tumor cells is poorly understood and is the focus of our lab.

Our data, based on the analysis of different cell lines derived from highly invasive human breast carcinomas support a general kiss-and-run exocytic mechanism of MT1-MMP at invadopodia. We identified several components of this exocytic machinery. We are also investigating the function of microtubules, tubulin post-translational modifications and microtubule motors during tumor cell invasion.

Finally, we developed an intraductal orthotopic xenograft model that we are using to study the cellular mechanisms underlying the transition from ductal carcinoma in situ to infiltrating lesions.

Figure 1 : Exoxytosis of MT1-MMP-containing late endosomes at the invadopodial plasma membrane.

Figure 1 :
Exoxytosis of MT1-MMP-containing late endosomes at the invadopodial plasma membrane.

Figure 2 Progression of intraductal xenograft of DCIS.COM cells from in situ to invasive carcinoma

Figure 2
Progression of intraductal xenograft of DCIS.COM cells from in situ to invasive carcinoma

 

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