Current lab members:

• Dr Gaggioli Cédric, DR2 INSERM
• Dr Lopez Pascal, CRCN INSERM
• Miss Artieres Lydia (PhD)
• Dr Albrengues Jean, CRCN INSERM
• Miss Mousset Alexandra (Ph D)
• Dr Bourget Isabelle, IE INSERM
• Mr. Odet Quentin (IE, CDD) (3D-Hub-S platform)

Lab Alumni:

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 signalling pathway, in CAF cells, for matrix remodelling 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 signalling 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.

Current Projects

Top Publications

• Patient-derived tumor organoids: a new avenue for preclinical research and precision medicine in oncology
  30 juin 2024 par Lucie Thorel
  Over the past decade, the emergence of patient-derived tumor organoids (PDTOs) has broadened the repertoire of preclinical models and progressively revolutionized three-dimensional cell culture in oncology. PDTO can be grown from patient tumor samples with high efficiency and faithfully recapitulates the histological and molecular characteristics of the original tumor. Therefore, PDTOs can serve as invaluable tools in oncology research, and their translation to clinical practice is exciting for…
• NETscape or NEThance: tailoring anti-cancer therapy
  25 avril 2024 par Alexandra Mousset
  Neutrophils, major regulators of innate immunity, have recently emerged as key components of the tumor microenvironment. The role of neutrophils in cancer has been linked to their ability to form neutrophil extracellular traps (NETs), structures composed of decondensed DNA decorated with enzymes that are released into the extracellular space. Here, we discuss the pivotal roles of NETs in influencing responses to anticancer therapies such as chemotherapy, radiotherapy, immunotherapy, and targeted…
• Neutrophil extracellular traps formed during chemotherapy confer treatment resistance via TGF-β activation
  29 novembre 2023 par Alexandra Mousset
  No abstract
• Neutrophil extracellular traps formed during chemotherapy confer treatment resistance via TGF-β activation
  10 avril 2023 par Alexandra Mousset
  Metastasis is the major cause of cancer death, and the development of therapy resistance is common. The tumor microenvironment can confer chemotherapy resistance (chemoresistance), but little is known about how specific host cells influence therapy outcome. We show that chemotherapy induces neutrophil recruitment and neutrophil extracellular trap (NET) formation, which reduces therapy response in mouse models of breast cancer lung metastasis. We reveal that chemotherapy-treated cancer cells…
• Secretion of IL1 by Dedifferentiated Melanoma Cells Inhibits JAK1-STAT3-Driven Actomyosin Contractility of Lymph Node Fibroblastic Reticular Cells
  3 mai 2022 par Christopher Rovera
  Fibroblastic reticular cells (FRC) are immunologically specialized myofibroblasts that control the elasticity of the lymph node, in part through their contractile properties. Swelling of tumor-draining lymph nodes is a hallmark of lymphophilic cancers such as cutaneous melanoma. Melanoma displays high intratumoral heterogeneity with the coexistence of melanoma cells with variable differentiation phenotypes from melanocytic to dedifferentiated states. Factors secreted by melanoma cells promote…
• Mesenchymal Stem Cells and PRP Therapy Favorize Leak Closure After Sleeve Gastrectomy in Zucker Rats
  23 février 2022 par Marine Benois
  CONCLUSION: These results suggest that PRP and MSCs may accelerate the closure of leaks following SG in rats and may become a new tool in the treatment of human gastric leaks but more research on this topic is needed to confirm these findings.
• Targeting Discoidin Domain Receptors DDR1 and DDR2 overcomes matrix-mediated tumor cell adaptation and tolerance to BRAF-targeted therapy in melanoma
  27 décembre 2021 par Ilona Berestjuk
  Resistance to BRAF/MEK inhibitor therapy in BRAF^(V600) -mutated advanced melanoma remains a major obstacle that limits patient benefit. Microenvironment components including the extracellular matrix (ECM) can support tumor cell adaptation and tolerance to targeted therapy; however, the underlying mechanisms remain poorly understood. Here, we investigated the process of matrix-mediated drug resistance (MMDR) in response to BRAF^(V600) pathway inhibition in melanoma. We demonstrate that physical…
• A Novel Screen for Expression Regulators of the Telomeric Protein TRF2 Identified Small Molecules That Impair TRF2 Dependent Immunosuppression and Tumor Growth
  2 juillet 2021 par Mounir El Maï
  Telomeric repeat-binding factor 2 (TRF2) is a subunit of the shelterin protein complex, which binds to and protects telomeres from unwanted DNA damage response (DDR) activation. TRF2 expression plays a pivotal role in aging and cancer, being downregulated during cellular senescence and overexpressed during oncogenesis. Cancers overexpressing TRF2 often exhibit a poor prognosis. In cancer cells, TRF2 plays multiple functions, including telomere protection and non-cell autonomous roles, promoting…
• A Feed-Forward Mechanosignaling Loop Confers Resistance to Therapies Targeting the MAPK Pathway in BRAF-Mutant Melanoma
  18 mars 2020 par Christophe A Girard
  Aberrant extracellular matrix (ECM) deposition and stiffening is a physical hallmark of several solid cancers and is associated with therapy failure. BRAF-mutant melanomas treated with BRAF and MEK inhibitors almost invariably develop resistance that is frequently associated with transcriptional reprogramming and a de-differentiated cell state. Melanoma cells secrete their own ECM proteins, an event that is promoted by oncogenic BRAF inhibition. Yet, the contribution of cancer cell-derived ECM…
• STAT3 targeting in dystrophic epidermolysis bullosa
  2 novembre 2019 par V R Mittapalli
  No abstract
• Mechanical forces rewire metabolism in the tumor niche
  28 mai 2019 par Thomas Bertero
  Tumor niche extracellular matrix stiffening and tumor cell metabolic reprogramming are two fundamental mediators of tumor progression. We recently elucidated a mechanistic interconnection between mechanotransduction and tumor metabolic rewiring in cancer. We demonstrated a stiffness-dependent amino acid crosstalk between stromal and cancer cells that fuels tumor progression and metastatic spreading.
• UBTD1 is a mechano-regulator controlling cancer aggressiveness
  27 février 2019 par Stéphanie Torrino
  Ubiquitin domain-containing protein 1 (UBTD1) is highly evolutionary conserved and has been described to interact with E2 enzymes of the ubiquitin-proteasome system. However, its biological role and the functional significance of this interaction remain largely unknown. Here, we demonstrate that depletion of UBTD1 drastically affects the mechanical properties of epithelial cancer cells via RhoA activation and strongly promotes their aggressiveness. On a stiff matrix, UBTD1 expression is…
• Tumor-Stroma Mechanics Coordinate Amino Acid Availability to Sustain Tumor Growth and Malignancy
  9 octobre 2018 par Thomas Bertero
  Dysregulation of extracellular matrix (ECM) deposition and cellular metabolism promotes tumor aggressiveness by sustaining the activity of key growth, invasion, and survival pathways. Yet mechanisms by which biophysical properties of ECM relate to metabolic processes and tumor progression remain undefined. In both cancer cells and carcinoma-associated fibroblasts (CAFs), we found that ECM stiffening mechanoactivates glycolysis and glutamine metabolism and thus coordinates non-essential amino…
• Matrix Stiffening and EGFR Cooperate to Promote the Collective Invasion of Cancer Cells
  21 juillet 2018 par Eloise M Grasset
  In squamous cell carcinoma (SCC), tissue invasion by collectively invading cells requires physical forces applied by tumor cells on their surrounding extracellular matrix (ECM). Cancer-related ECM is composed of thick collagen bundles organized by carcinoma-associated fibroblasts (CAF) within the tumor stroma. Here, we show that SCC cell collective invasion is driven by the matrix-dependent mechano-sensitization of EGF signaling in cancer cells. Calcium (Ca^(2+)) was a potent intracellular…
• Three-Dimensional Cell Culture Conditions Affect the Proteome of Cancer-Associated Fibroblasts
  11 juillet 2018 par Regine C Tölle
  In vitro cell culture systems are an invaluable tool for cell biological research to study molecular pathways and to characterize processes critical in human pathophysiology. However, the experimental conditions in two-dimensional (2D) cell cultures often differ substantially from the in vivo situation, which continuously raises concerns about the reliability and conferrability of the obtained results. Three-dimensional (3D) cell cultures have been shown to closer mimic in vivo conditions and…
• p38MAPK builds a hyaluronan cancer niche to drive lung tumorigenesis
  24 décembre 2016 par Anna Brichkina
  Expansion of neoplastic lesions generates the initial signal that instigates the creation of a tumor niche. Nontransformed cell types within the microenvironment continuously coevolve with tumor cells to promote tumorigenesis. Here, we identify p38MAPK as a key component of human lung cancer, and specifically stromal interactomes, which provides an early, protumorigenic signal in the tissue microenvironment. We found that lung cancer growth depends on short-distance cues produced by the cancer…
• Membrane-bound ICAM-1 contributes to the onset of proinvasive tumor stroma by controlling acto-myosin contractility in carcinoma-associated fibroblasts
  1 décembre 2016 par Stephanie Bonan
  Acto-myosin contractility in carcinoma-associated fibroblasts leads to assembly of the tumor extracellular matrix. The pro-inflammatory cytokine LIF governs fibroblast activation in cancer by regulating the myosin light chain 2 activity. So far, however, how LIF mediates cytoskeleton contractility remains unknown. Using phenotypic screening assays based on knock-down of LIF-dependent genes in fibroblasts, we identified the glycoprotein ICAM-1 as a crucial regulator of stroma fibroblast…
• Fibroblast activation in cancer: when seed fertilizes soil
  31 juillet 2016 par Sanya-Eduarda Kuzet
  In solid cancers, activated fibroblasts acquire the capacity to provide fertile soil for tumor progression. Specifically, cancer-associated fibroblasts (CAFs) establish a strong relationship with cancer cells. This provides advantages to both cell types: whereas cancer cells initiate and sustain CAF activation, CAFs support cancer cell growth, motility and invasion. This results in tumor progression, metastasis and chemoresistance. Numerous studies have detailed the mechanisms involved in…
• Epigenetic switch drives the conversion of fibroblasts into proinvasive cancer-associated fibroblasts
  16 décembre 2015 par Jean Albrengues
  Carcinoma-associated fibroblasts (CAF) mediate the onset of a proinvasive tumour microenvironment. The proinflammatory cytokine LIF reprograms fibroblasts into a proinvasive phenotype, which promotes extracellular matrix remodelling and collective invasion of cancer cells. Here we unveil that exposure to LIF initiates an epigenetic switch leading to the constitutive activation of JAK1/STAT3 signalling, which results in sustained proinvasive activity of CAF. Mechanistically, p300-histone…
• Knock out of the BASIGIN/CD147 chaperone of lactate/H+ symporters disproves its pro-tumour action via extracellular matrix metalloproteases (MMPs) induction
  19 août 2015 par Ibtissam Marchiq
  BASIGIN/CD147/EMMPRIN is a multifunctional transmembrane glycoprotein strongly expressed in tumours. BASIGIN controls tumour metabolism, particularly glycolysis by facilitating lactic acid export through the two monocarboxylate transporters MCT1 and hypoxia-inducible MCT4. However, before being recognized as a co-carrier of MCTs, BASIGIN was described as an inducer of extracellular matrix metalloproteases (MMPs). Early on, a model emerged in which, tumour cells use the extracellular domain of…

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