News of the center

CRCI2 NA was proud to help supporting the EMBO Workshop "Persistent cancer cell: Molecular mechanisms, dynamic models towards therapy" that took place June 28- July 1st 2022 at Cavtat, Croatia, nearby Dubrovnic.

Seminars and Webinars at the CRCI²NA

The seminars / Webinars of the CRCI²NA take place every Thursday at 11:30 am in the Amphitheatre - Building IRS UN or in distanciel.
These seminars are an opportunity to receive renowned scientists invited to present their scientific research work, which could possibly open new collaborations. Seminars are a great opportunity to promote the scientific expertise of our laboratory.



June 30 - Webinar by Nadine Laguette (Institute of Human Genetics, Montpellier)

"Regulation of polyunsaturated fatty acids by STING: role in type I interferonopathies"

Concerted alteration of immune and metabolic homeostasis underlies several inflammation-related pathologies, ranging from metabolic syndrome to infectious diseases. Here, we explored the coordination of nucleic acid-dependent inflammatory responses and metabolic homeostasis. We reveal that the Stimulator of Interferon Genes (STING) protein regulates metabolic homeostasis through inhibition of the Fatty acid desaturase 2 (FADS2), a rate-limiting enzyme in polyunsaturated fatty acids (PUFAs) desaturation. STING ablation and agonist-mediated degradation increased FADS2 activity and led to the accumulation of PUFAs that drive thermogenesis. STING agonists directly activated FADS2, promoting metabolic alterations. PUFAs in turn inhibited STING, thereby regulating antiviral responses and contributing to resolve STING-associated inflammation. Thus, we have unveiled a negative regulatory feedback loop between STING and FADS2 that fine-tunes inflammatory responses. Our results highlight the role of metabolic alterations in human pathologies associated with aberrant STING activation and STING targeting therapies. Such implications will be discussed, notably for chronic inflammatory pathologies where STING activation has been involved.

June 9 - Webinar by Prof. Pirjo Laakkonen

"Tackling deadly brain tumors: From biological function to drug development"

Prof Pirjo Laakkonen Professor Pirjo Laakkonen is Principal Investigator of the Translational Cancer Medicine Research Program at the University of Helsinki Medical School, Finland. Her research focuses on tumor targeting and understanding the molecular mechanisms underlying tumor invasion and metastasis. She has identified several tumor localization peptides, which have been used for targeted delivery of drugs and nanodevices, as well as for the identification of novel tumor-associated biomarkers. Recent interests in his lab include the development of targeted therapies against malignant glioma and breast cancer brain metastasis based on vulnerabilities discovered in these diseases. Pirjo Laakkonen received her PhD in 1996 in molecular virology from the University of Helsinki, Finland. She spent four years as a post-doctoral fellow at the Burnham Institute (San Diego, CA, USA), working on tumor targeting in the laboratory of Dr. Erkki Ruoslahti, before founding her own research group at the University of Helsinki. She is also the founder and vice president of the Finnish Brain Tumor Research Association (FIBTRA). In addition to her research activities, Pirjo Laakkonen is the Director of the Laboratory Animal Center at the University of Helsinki.

May 12 - Webinar by Dr. Gaetano Gargiulo

"Cell states and fate transitions revealed by synthetic locus control regions"

Dr Gaetano Gargiulo Glioblastoma is heterogeneous and incurable. We have recently developed a technology to design synthetic reporters that reflect the transcriptional output of tumor cell states and signaling pathway activity. This method is generally applicable to study homeostasis in normal tissues and diseases. Using our published data, I will discuss our findings in glioblastoma, where synthetic gene tracing establishes a causal link between cellular and molecular heterogeneity and therapeutic responses. From our unpublished data, I will show our novel method of designing synthetic locus control regions for any cellular entity or condition of interest, and present successful examples.

April 28 - Webinar by Lisa Nocquet PhD student Team 7

"Metabolic influence of cancer-associated fibroblasts on triple negative breast cancer cells sensitivity to apoptosis
Triple-negative breast cancer (TNBC) is an aggressive cancer with a poor prognosis that is particularly resistant to cytotoxic chemotherapeutic treatments, notably due to over-expression of anti-apoptotic proteins. Here we show that, additional to intrinsic resistance, cancer cells acquire resistance to apoptosis thanks to a dialogue with cancer-associated fibroblasts (CAFs) of the microenvironment."

Lisa Nocquet We used BH3-mimetics (e.g. ABT-737) targeting anti-apoptotic proteins of the BCL-2 family as cell death inducers in the TNBC cell line MDA-MB-468 cultured with conditioned-media of primary culture of CAFs from patients with invasive carcinoma. We established a cross-talk relying on soluble metabolic mediators. By analyzing metabolic phenotypic profiles, we noted enhanced consumption of mitochondria-fueling metabolites in MDA-MB-468 cancer cells under CAFs influence. CAFs promote oxygen consumption by cancer cells while a supply of pyruvate is sufficient to reduce cancer cells sensitivity to ABT-737-induced apoptosis. This suggests a central role of pyruvate in the protective effect of CAFs on TNBC cells apoptosis. Consistently, we show that CAFs protective effect is reversed by the inhibition of the mitochondrial entry of pyruvate in cancer cells.
We thus established a link between pyruvate metabolism and apoptosis resistance which allows TNBC cells to exploit CAF metabolic properties and unravelled a new potential therapeutic target to improve TNBC cytotoxic treatment in an ecosystemic context.

April 14 - Webinar by Dr. Didier Jean

"Molecular Heterogeneity in Malignant Pleural Mesothelioma"

 Dr. Didier Jean Malignant pleural mesothelioma is a thoracic cancer with a very poor prognosis and is a major public health problem. The presentation will provide an overview of the molecular alterations and specificities of the mesothelioma tumor. Particular emphasis will be placed on the molecular heterogeneity of mesothelioma and will give clues on how to take it into account in the perspective of precision medicine for this pathology.

April 7 - Webinar by Dr. Guillaume Van Niel, Institut Psychiatrie et Neuroscience Paris

"Basic lessons and therapeutic applications of live imaging of extracellular vesicles in vivo"

Dr. Guillaume Van Niel

March 3 - Webinar by Dr. Marc Billaud Co-leader of the Tumor Metabolic Targeting theme in the "Cell Death and Pediatric Cancers", team Director of the Human and Social Sciences Department of the Léon Bernard Center, member of the Expert Committee of the Aviesan Cancer ITMO, Cancer Research Center of Lyon

"Precision oncology : challenges and promises"

Dr. Marc Billaud Precision oncology, which classically combines the identification of molecular anomalies in tumors and the design of drugs targeting the product of these alterations, is often presented as a therapeutic revolution. However, even if this approach has transformed the prognosis of certain cancers, its development and transfer to clinical routine is confronted with numerous epistemological, medical, economic and social obstacles. The question of the stakes and limits of precision oncology will be the subject of this seminar.

January 25 - Webinar by Dr. Stephanie Torrino, IPMC Nice

"Post-translational modifications : Key players in cell mechanics"

Dr. Stephanie Torrino Cell mechanics is a fundamental determinant of cell and tissue shaping. Dr. Torrino has acquired a solid experience in the study of post-translational modifications (PTM), cellular metabolism and mechanobiology. Since the beginning of her career, she has used and adapted mechanical devices to explore the involvement of mechanical forces on post-translational modification pathways such as ubiquitinylation and SUMOylation. She is now tackling a new challenge by studying the glutamylation pathway (PTM that adds a variable number of glutamate residues as secondary branches of the protein) in cell mechanics. In particular, she has shown that matrix rigidification reorganizes glutamine metabolism to promote microtubule glutamylation and force microtubule stabilization, thereby promoting cell mechanics and tumor progression.

January 6 - Webinar by Jean-Baptiste Alberge, post-doctoral fellow at DANA-FARBER Cancer Institute - Boston

"Non-invasive liquid biopsy to characterize circulating tumor cells in precursor and overt multiple myeloma"

Jean-Baptiste Alberge Bone marrow (BM) biopsy is the gold standard for diagnosis and follow-up of multiple myeloma (MM), but it is intrusive, painful, and comes with potential secondary complications for patients. Therefore, repeated assessment is not a feasible option for screening and monitoring precursor patients who are asymptomatic. We show the feasibility of characterizing circulating tumor cells (CTCs) from a noninvasive blood biopsy to accompany BM as a method of monitoring disease development. CTCs were detected in 27% of collected patients with monoclonal gammopathy of undetermined significance (MGUS), in 57% of patients with smoldering multiple myeloma (SMM), and correlated with clinical disease measurement, including the International Myeloma Working Group 2/20/20 risk stratification model. Downstream molecular characterization confirms MM-associated genetic alterations and tumor origin of CTCs. Molecular analyses of CTCs were performed in patients with matching bone marrow and clinical fluorescent in situ hybridization (FISH) results. CTCs captured 100% of the BM copy number variation (CNV) events annotated clinically by FISH. In addition, CTC samples identified additional yield, with additional CNVs identified that had not been observed by FISH. In cases that did not have BM biopsy results, sequencing of CTCs revealed the existence of genetic aberrations. Our results demonstrate the clinical correlation and molecular characterization of CTCs from patients with precursor and manifest MM. Our study lays the foundation for non-invasive detection, enumeration, and genomic interrogation of rare peripheral blood CTCs, illustrating the clinical potential of using liquid biopsies for disease monitoring and management in the precursor MM setting.