Mechano-Oncology

Our goal is to understand the roles of mechanical signals generated at the interface between membrane and cytoskeleton during tumor-associated biological events.

This way of thinking about cancer is directly linked to the field of mechanobiology (i.e. the study of the role of mechanical forces in biological events) and to the lack of knowledge on the potential role of physical forces and parameters during tumor progression.

3 Axis of research:
A) Supporting tissues (stroma) with the study of fibroblast-matrix interaction.

The idea is to focus on the cells that surround tumors rather than the tumor itself. In a way it's like trying to build a wall and isolate the tumor cells rather than trying to work on the tumor cell. Fibroblast are the main "builders" of our body and numerous tumor are encapsided by matrix build by tumor associated fibroblasts. A better knowledge of the biophysical properties of those cells could potentially be beneficial to understand better tumor growth and metastasis.
Selected publications on this axis of research:

1. Pontes B, Monzo P, Gole L, Le Roux AL, Kosmalska AJ, Tam ZY, Luo W, Kan S, Viasnoff V, Roca-Cusachs P, Tucker-Kellogg L, Gauthier NC. Membrane tension controls adhesion positioning at the leading edge of cells. J Cell Biol. 2017 Jul 7. pii: jcb.201611117. doi: 10.1083/jcb.201611117.
2. Guetta-Terrier C, Monzo P, Zhu J, Long H, Venkatraman L, Zhou Y, Wang P, Chew SY, Mogilner A, Ladoux B, Gauthier NC. Protrusive waves guide 3D cell migration along nanofibers. J Cell Biol. 2015 Nov 9;211(3):683-701. See also biosight video from the Journal of Cell Biology: "Cells migrate on the crest of a wave".
3. Kosmalska AJ, Casares L, Elosegui-Artola A, Thottacherry JJ, Moreno-Vicente R, González-Tarragó V, del Pozo MÁ, Mayor S, Arroyo M, Navajas D, Trepat X, Gauthier NC, Roca-Cusachs P. Physical principles of membrane remodelling during cell mechanoadaptation. Nat Commun. 2015 Jun 15;6:7292.
4. Gauthier NC, Fardin MA, Roca-Cusachs P, Sheetz MP. Temporary increase in plasma membrane tension coordinates the activation of exocytosis and contraction during cell spreading. Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14467-72.

B) Immune function with the study of macrophage biomechanics.

Phagocytosis is an innate immune response where large changes in cell shape occur implying tremendous modifications of membrane and cytoskeleton organization. Tumor infiltration by macrophages is a hallmark of many tumors and understanding how macrophages behave and evolve with tumor progression could help to design new strategies to fight cancer.
Selected publications on this axis of research:

1. Masters TA, Sheetz MP, Gauthier NC. F-actin waves, actin cortex disassembly and focal exocytosis driven by actin-phosphoinositide positive feedback. Cytoskeleton (Hoboken). 2016 Apr;73(4):180-96.
2. Masters TA, Pontes B, Viasnoff V, Li Y, Gauthier NC. Plasma membrane tension orchestrates membrane trafficking, cytoskeletal remodeling, and biochemical signaling during phagocytosis. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):11875-80.

C) Brain cancer progression with the study of glioblastoma invasive properties.

In this axis of research, we are tackling directly one of the most devastating cancer, the glioblastoma. The survival rate of this cancer rarely exceed one year after the first diagnosis. It’s a challenging tumor because it spread and migrate rapidly. We think that looking at it with biophysical tools may unveil new potential axis to circumcise tumor progression and eventually help patient survival.
Selected publications on this axis of research:

1. Monzo P, Chong YK, Guetta-Terrier C, Krishnasamy A, Sathe SR, Yim EK, Ng WH, Ang BT, Tang C, Ladoux B, Gauthier NC, Sheetz MP. Mechanical confinement triggers glioma linear migration dependent on formin FHOD3. Mol Biol Cell. 2016 Apr 15;27(8):1246-61.
2. Guetta-Terrier C, Monzo P, Zhu J, Long H, Venkatraman L, Zhou Y, Wang P, Chew SY, Mogilner A, Ladoux B, Gauthier NC. Protrusive waves guide 3D cell migration along nanofibers. J Cell Biol. 2015 Nov 9;211(3):683-701.
3. Beadle C, Assanah MC, Monzo P, Vallee R, Rosenfeld SS, Canoll P. The role of myosin II in glioma invasion of the brain. Mol Biol Cell. 2008 Aug;19(8):3357-68.

Collaborations

2018.02.21 rel.02