Publications

Publications

Invadopodia Are Required for Cancer Cell Extravasation and Are a Therapeutic Target for Metastasis

By:
Contributors: John D. Lewis Research Group, Katia Carmine-Simmen, PhD, Konstantin Stoletov, PhD

Cell Rep. 2014 Sep 11;8(5):1558-70. doi: 10.1016/j.celrep.2014.07.050. Epub 2014 Aug 28.

Leong HS1, Robertson AE1, Stoletov K2, Leith SJ1, Chin CA1, Chien AE1, Hague MN3, Ablack A1, Carmine-Simmen K2, McPherson VA1, Postenka CO3, Turley EA4, Courtneidge SA5, Chambers AF3, Lewis JD6.

 

Abstract
Tumor cell extravasation is a key step during cancer metastasis, yet the precise mechanisms that regulate this dynamic process are unclear. We utilized a high-resolution time-lapse intravital imaging approach to visualize the dynamics of cancer cell extravasation in vivo. During intravascular migration, cancer cells form protrusive structures identified as invadopodia by their enrichment of MT1-MMP, cortactin, Tks4, and importantly Tks5, which localizes exclusively to invadopodia. Cancer cells extend invadopodia through the endothelium into the extravascular stroma prior to their extravasation at endothelial junctions. Genetic or pharmacological inhibition of invadopodia initiation (cortactin), maturation (Tks5), or function (Tks4) resulted in an abrogation of cancer cell extravasation and metastatic colony formation in an experimental mouse lung metastasis model. This provides direct evidence of a functional role for invadopodia during cancer cell extravasation and distant metastasis and reveals an opportunity for therapeutic intervention in this clinically important process.

PubMed

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Post-Doctoral Fellow Dr. Lian Willetts shines light on the frontiers of discovery

Dr. Lian Willetts was awarded 2nd place in the Falling Walls Lab Finale in Berlin representing Dr. John Lewis’ lab by presenting: “Breaking the Walls of Prostate Cancer Metastasis”

Lab Falling Walls is an international competition that challenges graduate students to showcase how their research is redefining their respective fields and breaking down the walls to the next major scientific breakthrough. The University of Alberta is one of 20 approved international events, and the Sept. 30 event saw 16 outstanding examples of graduate research. Dr. Willetts was awarded 1st place during this night.

International Labs and the Finale in Berlin

Falling Walls Lab is a global scale event that takes place in different vibrant cities around the world throughout the year. The Falling Walls Lab Finale is held each year in Berlin on 8 November. The Finale gathers 100 participants, among them all winners of the international Labs.

- Catalina Vasquez