Basic Research Team  " Tumor-Stroma Crosstalk in Invasive Cancer "

Dr Cédric GAGGIOLI,  Team Leader



In primary tumors, cancer cells are immersed in a complex microenvironment network comprising numerous cells, including carcinoma associated fibroblasts (CAF). Tumor-stroma crosstalk plays a major role in carcinoma development and invasion. We have previously demonstrated the crucial role of Janus Kinase dependent signaling pathway, in CAF cells, for matrix remodeling and tracks formation for cancer cells to invade. However, how “normal” resident fibroblasts are converted into pro-invasive CAF cells remains an open question. Malignant cells themselves promotes carcinogenesis through cytokines and growth factors secretion that influence stroma cells behaviour, which in return influence carcinoma cells invasion and malignancy. In line with our previous research, we aim at uncovered signaling pathways and molecules that govern stromal fibroblasts and carcinoma cells crosstalk during invasion, which could lead to the identification of therapeutic target for aggressive and metastatic cancer.

Research Project

Research Project

The project presents two major axes focused on :

Investigation of the signaling pathways that in SCC cells mediates the pro-invasive conversion of resident fibroblasts

We aim at identifying pathway in pro-invasive CAFs conversion from primary human dermal fibroblasts (HPF) isolated

from children foreskin. Using in vitro matrix remodeling and three-dimensional organotypic invasion assay.

Uncovering the signaling molecules secreted by pro-invasive “activated” fibroblasts that leads to SCC cells invasion

We aim at identifying matrix proteins differentially assemble within the matrix by stimulated HDF cells compare to their non-stimulated counterpart. A comparative proteomic approach will be used to qualitatively and quantitatively identify matrix proteins assembled within the matrix of stimulated HDF cells compared to the non-stimulated counterpart. Matrix molecules layered down by activated HDF cells to culture Petri dishes will be analyzed and identified using a mass spectrometry approach. The possible role that matrix components, selected on the basis of data published in the literature, may have on SCC cell behaviour will then be assessed by conventional cell biology procedures, which include cell adhesion, migration and invasion in three dimensional organotypic assays. This approach is expected to lead to the identification of secreted molecules involved in SCC cell invasion induced by CAF.

The proposed research projects aim at address fundamental aspects on invasive carcinoma development with a particular attention on the stroma as therapeutic target. Besides this contribution this project aims at identifying potential clinical target in a long-term goal for developing new strategies to counteract cancer cell invasion and metastasis.

Research Team

Research Team

GAGGIOLI Cedric, CR1 Inserm, Team Leader
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BOURGET Isabelle, IE1 Inserm
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GRASSET Eloïse, PhD Student

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KUZET Sanya, PhD Student

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LACOUR Jean-Philippe, PU-PH CHU Nice
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LECACHEUR Margaux, M2 Student

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MENEGUZZI Guerrino, DREM Inserm Emeritus
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Brichkina A, Bertero T, Loh HM, Nguyen NT, Emelyanov A, Rigade S, Ilie M, Hofman P, Gaggioli C, Bulavin DV.

p38MAPK builds a hyaluronan cancer niche to drive lung tumorigenesis.

Genes Dev. 2016 Dec 1;30(23):2623-2636.

Bonan S, Albrengues J, Grasset E, Kuzet SE, Nottet N, Bourget I, Bertero T, Mari B, Meneguzzi G, Gaggioli C.

Membrane-bound ICAM-1 contributes to the onset of proinvasive tumor stroma by controlling acto-myosin contractility in carcinoma-associated fibroblasts.

Oncotarget. 2017 Jan 3;8(1):1304-1320.


Albrengues J, Bertero T, Grasset E, Bonan S, Maiel M, Bourget I, Philippe C, Herraiz Serrano C, Benamar S,

Croce O, Sanz-Moreno V, Meneguzzi G, Feral CC, Cristofari G, Gaggioli C.

Epigenetic switch drives the conversion of fibroblasts into proinvasive cancer-associated fibroblasts.

Nat Commun., 2015, Dec 15;6:10204.

Marchiq I, Albrengues J, Granja S, Gaggioli C, Pouysségur J, Simon MP.

Knock out of the BASIGIN/CD147 chaperone of lactate/H+ symporters disproves its pro-tumour action

via extracellular matrix metalloproteases (MMPs) induction.

Oncotarget., 2015, Sep 22;6(28):24636-48.

Golan T, Messer AR, Amitai-Lange A, Melamed Z, Ohana R, Bell RE, Kapitansky O, Lerman G, Greenberger S,

Khaled M, Amar N, Albrengues J, Gaggioli C, Gonen P, Tabach Y, Sprinzak D, Shalom-Feuerstein R, Levy C.

Interactions of Melanoma Cells with Distal Keratinocytes Trigger Metastasis via Notch Signaling Inhibition of MITF.

Mol Cell., 2015, Aug 20;59(4):664-76.

Masuzzo P, Martens L; 2014 Cell Migration Workshop Participants, Ampe C, Anderson KI, Barry J, De Wever O,

Debeir O, Decaestecker C, Dolznig H, Friedl P, Gaggioli C, Geiger B, Goldberg IG, Horn E, Horwitz R, Kam Z,

Le Dévédec SE, Vignjevic DM, Moore J, Olivo-Marin JC, Sahai E, Sansone SA, Sanz-Moreno V, Strömblad S,

Swedlow J, Textor J, Van Troys M, Zantl R.

An open data ecosystem for cell migration research.

Trends Cell Biol., 2015, Feb;25(2):55-8.


Orgaz JL, Pandya P, Dalmeida R, Karagiannis P, Sanchez-Laorden B, Viros A, Albrengues J, Nestle FO,

Ridley AJ, Gaggioli C, Marais R, Karagiannis SN, Sanz-Moreno V.

Diverse matrix metalloproteinase functions regulate cancer amoeboid migration.

Nat Commun., 2014, Jun 25;5:4255.

Albrengues J, Bourget I, Pons C, Butet V, Hofman P, Tartare-Deckert S, Feral CC, Meneguzzi G, Gaggioli C.

LIF mediates proinvasive activation of stromal fibroblasts in cancer.

Cell Rep., 2014, Jun 12;7(5):1664-78.

Albrengues J, Meneguzzi G, Gaggioli C.

Carcinoma-associated fibroblasts in cancer: the great escape.

Med Sci (Paris), 2014, Apr;30(4):391-7.


Albrengues J, Meneguzzi G, Gaggioli C.

Analysis of collective invasion of carcinoma cells in a 3D organotypic model.

Methods Mol. Biol., 2013;961:243-52.


Shalom-Feuerstein R, Serror L, De La Forest Divonne S, Petit I, Aberdam E, Camargo L, Damour O,

Vigouroux C, Solomon A, Gaggioli C, Itskovitz-Eldor J, Ahmad S, Aberdam D.

Pluripotent stem cell model reveals essential roles for miR-450b-5p and miR-184 in embryonic

corneal lineage specification.

Stem Cells., 2012, May;30(5):898-909.


Sanz-Moreno V†, Gaggioli C†, Yeo M, Albrengues J, Wallberg F, Viros A, Hooper S, Mitter R, Féral CC,

Cook M, Larkin J, Marais R, Meneguzzi G, Sahai E, Marshall CJ.

ROCK and JAK1 signaling cooperate to control actomyosin contractility in tumor cells and stroma.

Cancer Cell., 2011, Aug16;20(2):229-45. †Contributed equally to this work.


Hooper S, Gaggioli C, Sahai E.

A chemical biology screen reveals a role for Rab21-mediated control of actomyosin contractility in

fibroblast-driven cancer invasion.

Br J Cancer., 2010, Jan 19;102(2):392-402.


Medjkane, S., Perez-Sanchez, C., Gaggioli, C, Sahai, E., and Treisman, R.

Myocardin-Related Transcription Factors and SRF are required for cytoskeletal dynamics, invasion

and experimental metastasis.

Nat Cell Biol, 2009, Mar;11(3):257-68.


Gaggioli C. 

Collective invasion of carcinoma cells: when the fibroblasts take the lead.

Cell Adh Migr., 2008, Jan-Mar;2(1):45-7.


Gaggioli C., Hooper H., Hidalgo-Carcedo C., Grosse R., Marshall JF., Harrington K., Sahai E.

Fibroblast led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading

and following cells.

Nat Cell Biol., 2007, Dec;9(12):1392-400.

Gaggioli C., Sahai E.

Melanoma Invasion: Current knowledge and future directions.

Pigment Cell Res. 2007, Jun;20 (3):161-72. Review.

Gaggioli C., Robert G., Bertolotto C., Bailet O., Abbe P., Spadafora A, Bahadoran P, Ortonne J-P,

Baron V, Ballotti R. & Tartare-Deckert, S.

Tumor-Derived Fibronectin Is Involved in Melanoma Cell Invasion and Regulated by

V600E B-Raf Signaling Pathway.

J Invest Dermatol., 2007, Feb;127(2):400-10.


Guillaume Robert, Cédric Gaggioli, Carine Chavey, Olivier Bailet, Patricia Abbe, Edith Aberdam,

Sabatie Emillie, Amparo Cano, Garcia De Herreros, Robert Ballotti, Sophie Tartare-Deckert.

SPARC represses E-cadherin expression and induces mesenchymal transition during melanoma


Cancer Research, 2006, Aug 1;66(15):7516-23.


Roser Buscà, Edurne Berra, Cédric Gaggioli, Barbara Marchetti, Raphaël Thyss, Giorgos Fitsialos,

Mehdi Khaled, Lionel Larribère, Corine Bertolotto, Thierry Virolle, Pascal Barbry, Jacques Pouysségur,

Gilles Ponzio, Robert Ballotti.

Hypoxia Inducible Factor 1 alpha is a new target of Microphthalmia Associated Transcription

Factor (MITF) in melanoma cells.

J Cell Biol., 2005, Jul 4;170(1):49-59.

Gaggioli C. Deckert M., Robert G., Abbe P., Batoz M., Ehrengruber M.U., Ortonne J-P, Ballotti R.,

Tartare-Deckert, S.

HGF induces fibronectin matrix synthesis in melanoma cells through MAP kinase-dependent

signaling pathway and induction of Egr-1.

Oncogene, 2005, Feb 17;24(8):1423-33.

Marella M, Gaggioli C, Batoz M, Deckert M, Tartare-Deckert S & Chabry J.

Pathological prion protein exposure switches on neuronal MAP-kinase pathway resulting in

microglia recruitment.

J Biol Chem., 2005, Jan14;280(2):1529-34.


Cédric Gaggioli, Roser Buscà, Patricia Abbe, Jean-Paul Ortonne, Robert Ballotti.

Expression of Microphthalmia-associated Transcription Factor (MITF) is Required but does not Induce

Melanogenesis in mammalian melanocytic cells.

Pigment Cell Res., 2003, Aug;16(4):374-82.

(Feb 2016)