Team: Tumor microenvironnement and resistance to treatment – Oct 2021 CFATG
Team: Tumor microenvironnement and resistance to treatment – Oct 2021

Team: Tumor microenvironnement and resistance to treatment

Team presentation

Institut de Recherche en Cancérologie de Montpellier (U1194)
Campus Val d’Aurelle
208 avenue des Apothicaires
34298 Montpellier cedex 5 FRANCE
Tel : 33.(0)4.67.61.85.77
FAX : 33.(0)4.67.61.37.87

Website : https://www.ircm.fr/index.php?pagendx=1146

Team Leader : Andrei Turtoï

PI of the autophagy project: Sophie Pattingre (CRCN, INSERM, sophie.pattingre@inserm.fr)

Team members :
Sophie Pattingre (CRCN, INSERM)
Andrei Turtoï (CRCN, INSERM, Chef d’équipe)
Marie-Alix Poul (PU, Université de Montpellier 2)
Didier Pourquier (Pathologiste, ICM, Montpellier)

Other persons involved in the project: Evelyne Crapez (URT, IRCM,, Montpellier), Florence Boissière (URT, IRCM, Montpellier)


From the left to the right : Sophie Pattingre (CRCN, INSERM), Andrei Turtoi (CRCN, INSERM), Marie-Alix Poul (PU, Université de Montpellier 2).

Keywords: Autophagy, Tumoral microenvironment, Mitophagy, Resistance, Cancer

Research Topic :
Our team is interested in the role of the microenvironment in the tumor aggressiveness and response to anti-cancer treatments. They are many actors in the tumor stroma including cancer-associated fibroblasts, endothelial and immune cells. Characterization of immune cells (immunoscore) is now used for prognosis or prediction of response to therapy while the targeting of endothelial cells with anti-VEGF is commonly used in the clinic. However, it remains a neglected element in cancer research since within the tumor, nerves are intimately linked to the cancer cells. The interaction between tumor cells and neurons is a sign of tumor aggressiveness and resistance to chemotherapy or radiotherapy. Their presence within the tumor is a diagnostic element used routinely by pathologists. Thanks to a close collaboration with the Pathology Department of the Cancer Institute of Montpellier (ICM), we are studying the role of autophagy in the interaction between cancer cells and neurons in order to understand the mechanics of this interaction and its role in the response to radiotherapy in colorectal cancer.
In parallel to these translational studies, we are studying the mechanism of mitophagy regulation in cancer cells. We have shown that the co-chaperone BAG6 is essential for mitophagy. We determined the mechanism and showed that (1) BAG6 induces mitochondrial fission, a prerequisite for mitophagy, (2) BAG6 stimulates the PINK1/PARKIN pathway and finally (3) via an LIR domain, the interaction between BAG6 and LC3 is essential for mitophagy, suggesting that BAG6 is a novel receptor for selective autophagy (Ragimbeau et, 2021).


BAG6 stimulates mitophagy by allowing mitochondrial fission and by stimulating PINK1/PARKIN activity. Moreover, via an LIR (LC3 Interacting Region) domain, the interaction between BAG6 and LC3 is essential for mitophagy suggesting that BAG6 is a novel receptor for mitophagy.

References :
BAG6 promotes PINK1 signaling pathway and is essential for mitophagy. Ragimbeau R, El Kebriti L, Sebti S, Fourgous E, Boulahtouf A, Arena G, Espert L, Turtoi A, Gongora C, Houédé N, Pattingre S. FASEB J. 2021.
Metastatic colorectal cancer cells maintain the TGFβ program and use TGFBI to fuel angiogenesis. Chiavarina B, Costanza B, Ronca R, Blomme A, Rezzola S, Chiodelli P, Giguelay A, Belthier G, Doumont G, Van Simaeys G, Lacroix S, Yokobori T, Erkhem-Ochir B, Balaguer P, Cavailles V, Fabbrizio E, Di Valentin E, Gofflot S, Detry O, Jerusalem G, Goldman S, Delvenne P, Bellahcène A, Pannequin J, Castronovo V, Turtoi A. Theranostics. 2021. 11:1626-1640.
Paracrine interactions of cancer-associated fibroblasts, macrophages and endothelial cells: tumor allies and foes. Ronca R, Van Ginderachter JA, Turtoi A. Curr Opin Oncol. 2018. 30:45-53.
Murine stroma adopts a human-like metabolic phenotype in the PDX model of colorectal cancer and liver metastases. Blomme A, Van Simaeys G, Doumont G, Costanza B, Bellier J, Otaka Y, Sherer F, Lovinfosse P, Boutry S, Palacios AP, De Pauw E, Hirano T, Yokobori T, Hustinx R, Bellahcène A, Delvenne P, Detry O, Goldman S, Nishiyama M, Castronovo V, Turtoi A.Oncogene. 2018. 37:1237-1250.
BAG6/BAT3 modulates autophagy by affecting EP300/p300 intracellular localization. Sebti S, Prébois C, Pérez-Gracia E, Bauvy C, Desmots F, Pirot N, Gongora C, Bach AS, Hubberstey AV, Palissot V, Berchem G, Codogno P, Linares LK, Liaudet-Coopman E, Pattingre S. Autophagy. 2014. 1341-2.
BAT3 modulates p300-dependent acetylation of p53 and autophagy-related protein 7 (ATG7) during autophagy. Sebti S, Prébois C, Pérez-Gracia E, Bauvy C, Desmots F, Pirot N, Gongora C, Bach AS, Hubberstey AV, Palissot V, Berchem G, Codogno P, Linares LK, Liaudet-Coopman E, Pattingre S. Proc Natl Acad Sci U S A. 2014. 111:4115-20.

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