Title :

ProNGF promotes brain metastasis through TrkA/EphA2 induced Src activation in triple negative breast cancer cells

Author(s) :

Cicero, Julien [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Laboratoire de la Barrière Hémato-Encéphalique [LBHE]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]
Université d'Artois [UA]
Trouvilliez, Sarah [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Palma, Martine [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Ternier, Gaetan [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Decoster, Laurine [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Happernegg, Eloise [Auteur]
Laboratoire de la Barrière Hémato-Encéphalique [LBHE]
Université d'Artois [UA]
Barois, Nicolas [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Van Outryve, Alexandre [Auteur]
Dehouck, Lucie [Auteur]
Laboratoire de la Barrière Hémato-Encéphalique [LBHE]
Université d'Artois [UA]
Bourette, Roland [Auteur]
Institut de biologie de Lille - IBL [IBLI]
Adriaenssens, Eric [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Lagadec, Chann [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Tarhan, Cagatay [Auteur]
Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 [IEMN]
Bio-Micro-Electro-Mechanical Systems - IEMN [BIOMEMS - IEMN]
JUNIA [JUNIA]
Collard, Dominique [Auteur]
Laboratory for Integrated Micro Mechatronics Systems [LIMMS]
JUNIA [JUNIA]
Souguir, Zied [Auteur]
Vandenhaute, Elodie [Auteur]
Maubon, Grégory [Auteur]
Sipieter, François [Auteur]
Institut Jacques Monod [IJM (UMR_7592)]
Borghi, Nicolas [Auteur]
Institut Jacques Monod [IJM (UMR_7592)]
Shimizu, Fumitaka [Auteur]
Yamaguchi University [Yamaguchi]
Kanda, Takashi [Auteur]
Giacobini, Paolo [Auteur]
Gosselet, Fabien [Auteur]
Laboratoire de la Barrière Hémato-Encéphalique [LBHE]
Université d'Artois [UA]
Maubon, Nathalie [Auteur]
Le Bourhis, Xuefen [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Van Seuningen, Isabelle [Auteur]
Mysiorek, Caroline [Auteur]
Université d'Artois [UA]
Laboratoire de la Barrière Hémato-Encéphalique [LBHE]
Toillon, Robert [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]

Journal title :

Experimental Hematology & Oncology

Pages :

104

Publisher :

BMC

Publication date :

2023-12-10

English keyword(s) :

proNGF
TrkA
EphA2
Src
Brain metastasis
Breast cancer

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Background Triple-Negative Breast Cancer is particularly aggressive, and its metastasis to the brain has a significant psychological impact on patients' quality of life, in addition to reducing survival. The development ...
Show more >Background Triple-Negative Breast Cancer is particularly aggressive, and its metastasis to the brain has a significant psychological impact on patients' quality of life, in addition to reducing survival. The development of brain metastases is particularly harmful in triple-negative breast cancer (TNBC). To date, the mechanisms that induce brain metastasis in TNBC are poorly understood. Methods Using a human blood-brain barrier (BBB) in vitro model, an in vitro 3D organotypic extracellular matrix, an ex vivo mouse brain slices co-culture and in an in vivo xenograft experiment, key step of brain metastasis were recapitulated to study TNBC behaviors. Results In this study, we demonstrated for the first time the involvement of the precursor of Nerve Growth Factor (proNGF) in the development of brain metastasis. More importantly, our results showed that proNGF acts through TrkA independent of its phosphorylation to induce brain metastasis in TNBC. In addition, we found that proNGF induces BBB transmigration through the TrkA/EphA2 signaling complex. More importantly, our results showed that combinatorial inhibition of TrkA and EphA2 decreased TBNC brain metastasis in a preclinical model. Conclusions These disruptive findings provide new insights into the mechanisms underlying brain metastasis with proNGF as a driver of brain metastasis of TNBC and identify TrkA/EphA2 complex as a potential therapeutic target.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Institut d'Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520

Source :

Harvested from HAL